ABSTRACT
BACKGROUND: The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS. METHODS: Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels. RESULTS: The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate. CONCLUSIONS: This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (TD = - 0.494TC-0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.
Subject(s)
Graft Rejection/drug therapy , Graft Survival/immunology , Immunosuppressive Agents/therapeutic use , Liver Transplantation/adverse effects , Tacrolimus/therapeutic use , Animals , Aspartate Aminotransferases/blood , Immunosuppressive Agents/blood , Liver/immunology , Liver Transplantation/methods , Living Donors , Organ Size/immunology , Rats , Rats, Inbred BN , Rats, Inbred Lew , Tacrolimus/blood , Transplants/immunology , Treatment OutcomeABSTRACT
American visceral leishmaniasis is caused by the protozoan Leishmania infantum. The control of the disease depends on the magnitude of the Th1 cell response and IL-10 producing regulatory T cells. Administration of chemokine, such as CXCL10, has shown promising results in the leishmaniasis treatment. Previous studies from our group have shown that CXCL10 induces a reduction in parasite burden in the spleen and a decrease in IL-10 and TGF-ß production in L. infantum-infected BALB/c mice. This work investigated whether CXCL10-treatment reduces IL-10 + Treg cell populations (CD4+CD25+Foxp3+ and Tr1) and induces morphological changes in the spleen. BALB/c mice were infected and treated or not with CXCL10 on the 1st, 3rd and 7th days of infection. CXCL10-treatment was able to reduce the parasite load in the spleen in L. infantum-infected BALB/c mice and this decrease in the number of parasites correlated with the decrease in size of this organ in treated animals compared to untreated animals. 7, 23, and 45 days post-treatment (p.t.), the phenotype and frequency of IL-10 + Treg cells were evaluated by flow cytometry, and the morphological changes of the spleen were analyzed by optical microscopy. After 7 and 23 days p.t., CXCL10-treated animals showed a significant reduction of CD25-Foxp3-IL-10+ (Tr1) cells in the spleen when compared to untreated animals, whereas CD4+CD25+Foxp3+IL-10+ Treg cells reduced later at 23rd and 45th days p.t. Furthermore, while untreated animals showed a significant positive correlation between IL-10 production and Tr1 cells, in CXCL10-treated group this correlation was negative. Thus, these findings show that treatment with CXCL10 chemokine in L. infantum-infected BALB/c mice results in suppression of IL10+ Treg (Foxp3+ and Tr1) cells in the spleen, associated with a reduction in parasite load and splenomegaly.
Subject(s)
Chemokine CXCL10/therapeutic use , Leishmaniasis, Visceral/drug therapy , Leishmaniasis, Visceral/immunology , Spleen/immunology , T-Lymphocytes, Regulatory/drug effects , Adjuvants, Immunologic/therapeutic use , Animals , Chemokine CXCL10/administration & dosage , Chemokine CXCL10/pharmacology , Cricetinae , Flow Cytometry , Forkhead Transcription Factors/immunology , Humans , Injections, Intraperitoneal , Leishmania infantum/drug effects , Leishmania infantum/immunology , Leishmania infantum/pathogenicity , Male , Mesocricetus , Mice , Mice, Inbred BALB C , Organ Size/drug effects , Organ Size/immunology , Parasite Load , Spleen/parasitology , Spleen/pathology , T-Lymphocytes, Regulatory/immunology , VirulenceABSTRACT
We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 µg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.
Subject(s)
Adrenal Glands/drug effects , Immunity, Innate/drug effects , Lipopolysaccharides/pharmacology , Stress, Psychological/physiopathology , Thymus Gland/drug effects , Adrenal Glands/physiopathology , Animals , Immobilization/methods , Injections, Intraperitoneal , Male , Organ Size/drug effects , Organ Size/immunology , Rats , Rats, Wistar , Spleen/drug effects , Spleen/physiopathology , Stress, Psychological/immunology , Stress, Psychological/prevention & control , Thymus Gland/physiopathologyABSTRACT
PURPOSE: To longitudinally evaluate the cortical thickness and deep gray matter structures volume, measured from T1 three-dimensional (3D) Gradient echo-weighted imaging, and white matter integrity, assessed from diffusion tensor imaging (DTI) of HIV-positive patients. MATERIALS AND METHODS: Twenty-one HIV-positive patients on stable highly active antiretroviral therapy (HAART) with CD4+ T lymphocytes count >200 cells/mL and viral load <50 copies/mL underwent two magnetic resonance imaging (MRI) scans with a median interval of 26.6 months. None of the patients had HIV-related dementia. T1 3D magnetization prepared rapid gradient echo-weighted imaging and DTI along 30 noncolinear directions were performed using a 1.5 Tesla MR scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of deep gray matter structures. For tract-based spatial statistics analysis, a white matter skeleton was created, and a permutation-based inference with 5000 permutations, with a threshold of P < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The median, radial, and axial diffusivities were also projected onto the mean FA skeleton. RESULTS: There were no significant differences in cortical thickness, deep gray matter structures volumes or diffusivity parameters between scans at the two time points (considering P < 0.05). CONCLUSION: No longitudinal differences in cortical thickness, deep gray matter volumes, or white matter integrity were observed in an HIV-positive population on stable HAART, with undetectable viral load and high CD4+ T lymphocytes count. J. Magn. Reson. Imaging 2016;44:1262-1269.
Subject(s)
Diffusion Tensor Imaging/methods , Encephalitis, Viral/drug therapy , Encephalitis, Viral/pathology , Gray Matter/pathology , HIV Infections/drug therapy , HIV Infections/pathology , White Matter/pathology , Adult , Antiretroviral Therapy, Highly Active/methods , Encephalitis, Viral/immunology , Female , Gray Matter/immunology , HIV Infections/immunology , Humans , Longitudinal Studies , Male , Middle Aged , Organ Size/immunology , Treatment Outcome , Viral Load/immunology , White Matter/immunologyABSTRACT
The effect of organic trace mineral supplementation on performance, intestinal morphology, immune organ weights (bursa of Fabricius and spleen), expression of innate immune response related genes, blood heterophils/lymphocytes ratio, chemical metabolic panel, natural antibodies (IgG), and oxidative stress of broiler chickens was studied. A total of 1,080 day-old male broilers were assigned to 1 of 3 dietary treatments, which included basal diet with Monensin (control), control diet supplemented with bacitracin methylene disalicylate (BMD), and BMD diet supplemented with organic trace minerals (OTM). No difference in feed conversion ratio was observed among treatments; ileum histomorphological analysis showed a lower crypt depth, higher villi height/crypt depth ratio, and lower villi width in the OTM treatment compared to control. Furthermore, OTM treatment resulted in higher uric acid and lower plasma malondehaldehyde (MDA), indicating lower oxidative stress. Gene expression analysis showed that OTM treatment resulted in up-regulations of TLR2 bin the ileum, and TLR2b, TLR4, and IL-12p35 in the bursa of Fabricius, and down-regulation of TLR2b and TLR4 in the cecal tonsils. In the spleen, OTM treatment resulted in up-regulation of IL-10. In conclusion, OTM supplementation to broiler diets may have beneficial effects on intestinal development, immune system status, and survival by improving ileum histomorphological parameters, modulation of Toll-like receptors and anti-inflammatory cytokines, and decreasing level of MDA, which in conjunction could enhance health status.
Subject(s)
Animal Nutritional Physiological Phenomena , Chickens/physiology , Diet/veterinary , Dietary Supplements , Immunity, Innate/immunology , Oxidative Stress/immunology , Animal Feed/analysis , Animals , Antibodies, Heterophile/blood , Chickens/anatomy & histology , Chickens/growth & development , Chickens/immunology , Immune System/growth & development , Immunoglobulin G/blood , Intestines/anatomy & histology , Lymphocyte Count/veterinary , Lymphocytes/immunology , Organ Size/immunology , Trace ElementsABSTRACT
Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M(2) muscarinic acetylcholine receptor (M(2)R). To elucidate the role of autoimmunity against M(2)R in disease development, we induced an immune response against M(2)R by adoptive transfer into Rag2(-/-) mice of splenocytes from M(2)R(-/-) mice immunized with a recombinant M(2)R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M(2)R, which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function, and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M(2)R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.
Subject(s)
Autoimmunity , Cardiomyopathy, Dilated/immunology , Disease Models, Animal , Myocarditis/immunology , Receptor, Muscarinic M2/immunology , Action Potentials/physiology , Animals , Autoantibodies/biosynthesis , Autoantibodies/immunology , Calcium Signaling/immunology , Cardiomyopathy, Dilated/pathology , Cardiomyopathy, Dilated/physiopathology , Cells, Cultured , Female , Immunoglobulin G/immunology , Male , Mice , Mice, Inbred C57BL , Myocarditis/pathology , Myocarditis/physiopathology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/pathology , Organ Size/immunology , Rats , Rats, Wistar , T-Lymphocytes/immunologyABSTRACT
Periodontitis is one of the most common infections in humans. Recently, published reports assert that periodontitis is associated with cardiovascular disease. Although it is said that viral, bacterial infections and autoimmune diseases may be the cause of myocarditis, the pathogenesis of it remains unclear. The aim of this study was to investigate the influence of a periodontal pathogen on experimental autoimmune myocarditis (EAM). Porphyromonas gingivalis (P.g.), PBS as a control, were injected into the mice. Histopathological and immunohistochemical analyses were performed. We examined heart mRNA levels using quantitative RT-PCR. The anti-P.g. IgG antibody level in plasma samples of the P.g.-injected group significantly increased compared with the PBS-injected group. Histopathological analysis detected that the myocarditis-affected areas and the fibrotic area in the P.g.-injected EAM group significantly increased compared with the PBS-injected EAM group (P < 0.05). Immunohistochemical analysis detected that more CD11b-positive cells were shown in the heart of the P.g.-injected EAM group compared with the PBS EAM-injected group (P < 0.05). Hearts from the P.g.-injected EAM group showed significantly increased expression of monocyte chemoattractant protein-1, IFN-γ, and matrix metalloproteinase-9 (MMP-9) mRNA compared with the hearts from the PBS-injected EAM group (P < 0.05). On day 7, serum levels of IL-6 were significantly enhanced in the P.g.-injected EAM group compared with the PBS-injected EAM group (P < 0.05). These results showed that P.g. injection could deteriorate EAM in mice through CD11b-positive cells, cytokines, and MMP-9 expression.
Subject(s)
Antibodies, Bacterial/blood , Autoantibodies/blood , Autoimmune Diseases/immunology , Myocarditis/immunology , Periodontitis/immunology , Porphyromonas gingivalis/immunology , Animals , Autoimmune Diseases/epidemiology , Autoimmune Diseases/microbiology , Body Weight , CD11b Antigen/immunology , Cytokines/blood , Cytokines/immunology , Disease Models, Animal , Lung/immunology , Lung/pathology , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/immunology , Mice , Mice, Inbred BALB C , Myocarditis/epidemiology , Myocarditis/microbiology , Myosins/immunology , Organ Size/immunology , Periodontitis/epidemiology , Periodontitis/microbiology , Prevalence , Risk Factors , Seroepidemiologic StudiesABSTRACT
Autism spectrum disorder (ASD) is very heterogeneous and multiple subtypes and etiologies likely exist. The maternal immune system has been implicated in the pathogenesis of some forms of ASD. Previous studies have identified the presence of specific maternal IgG autoantibodies with reactivity to fetal brain proteins at 37 and 73kDa in up to 12% of mothers of children with ASD. The current study evaluates the presence of these autoantibodies in an independent cohort of mothers of 181 preschool-aged male children (131 ASD, 50 typically developing (TD) controls). We also investigated whether ASD children born to mothers with these autism-specific maternal IgG autoantibodies exhibit a distinct neural phenotype by evaluating total brain volume using structural magnetic resonance imaging (MRI). Of the 131 ASD children, 10 (7.6%) were born to mothers with the 37/73kDa IgG autoantibodies (ASD-IgG). The mothers of the remaining ASD children and all TD controls were negative for these paired autoantibodies. While both ASD groups exhibited abnormal brain enlargement that is commonly observed in this age range, the ASD-IgG group exhibited a more extreme 12.1% abnormal brain enlargement relative to the TD controls. In contrast, the remaining ASD children exhibited a smaller 4.4% abnormal brain enlargement relative to TD controls. Lobar and tissue type analyses revealed that the frontal lobe is selectively enlarged in the ASD-IgG group and that both gray and white matter are similarly affected. These results suggest that maternal autoantibodies associated with autism spectrum disorder may impact brain development leading to abnormal enlargement.
Subject(s)
Autoantibodies/immunology , Brain/pathology , Child Development Disorders, Pervasive/immunology , Immunoglobulin G/immunology , Adult , Brain/immunology , Child Development Disorders, Pervasive/pathology , Child, Preschool , Female , Humans , Magnetic Resonance Imaging , Male , Organ Size/immunologyABSTRACT
1. The relative expression of heat shock protein (HSP) genes (HSP60, HSP70 and HSP90) was performed using quantitative real-time PCR on tissue from the heart ventricles to investigate the effect of 3,5,3'-l-triiodothyronine (T3)-induced pulmonary hypertension in broiler chickens. 2. The ratio of the right ventricle to total ventricle (index of pulmonary hypertension) was increased in the treated groups at 12 and 42 d of age compared to controls but was significant only at 42 d. 3. The HSP genes were expressed in the right and left ventricles of control but T3-treated broilers at 12 and 42 d of age. The relative amounts of HSP60 and HSP90 gene expression in the right ventricle of treated groups were significantly increased at 12 d and decreased at 42 d of age compared to controls. 4. Variations of HSP60 and HSP90 mRNAs in the left ventricle were not significant. The relative amount of HSP70 mRNA expression in the right and left ventricles of treated groups was significantly decreased at 42 d of age compared to controls. HSP70 mRNA expression did not differ between the right and left ventricles at 12 d of age. 5. It is concluded that gene expression of HSPs (i.e. HSP60 and HSP90) was upregulated in the heart of chickens developing pulmonary hypertension syndrome, probably to delay the pathological process of disease. The right ventricle from hearts of pulmonary hypertensive chickens showed considerable reductions of HSP60, HSP70 and HSP90, which is evidence of a loss of compensatory responsiveness in dilated heart.
Subject(s)
Chickens , Gene Expression Regulation/immunology , HSP70 Heat-Shock Proteins/immunology , HSP90 Heat-Shock Proteins/immunology , Heart Ventricles/immunology , Hypertension, Pulmonary/veterinary , Poultry Diseases/immunology , Animals , HSP70 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/genetics , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/immunology , Male , Organ Size/immunology , Poultry Diseases/genetics , RNA/chemistry , RNA/genetics , Random Allocation , Real-Time Polymerase Chain Reaction/veterinary , Triiodothyronine/administration & dosageABSTRACT
Erythropoietin-producing hepatocellular kinases (Eph kinases) constitute the largest family of cell membrane receptor tyrosine kinases, and their ligand ephrins are also cell surface molecules. Because of promiscuous interaction between Ephs and ephrins, there is considerable redundancy in this system, reflecting the essential roles of these molecules in the biological system through evolution. In this study, both Efnb1 and Efnb2 were null-mutated in the T cell compartment of mice through loxP-mediated gene deletion. Mice with this double conditional mutation (double KO mice) showed reduced thymus and spleen size and cellularity. There was a significant decrease in the DN4, double positive, and single positive thymocyte subpopulations and mature CD4 and CD8 cells in the periphery. dKO thymocytes and peripheral T cells failed to compete with their WT counterparts in irradiated recipients, and the T cells showed compromised ability of homeostatic expansion. dKO naive T cells were inferior in differentiating into Th1 and Th17 effectors in vitro. The dKO mice showed diminished immune response against LCMV infection. Mechanistic studies revealed that IL-6 signaling in dKO T cells was compromised, in terms of abated induction of STAT3 phosphorylation upon IL-6 stimulation. This defect likely contributed to the observed in vitro and in vivo phenotype in dKO mice. This study revealed novel roles of Efnb1 and Efnb2 in T cell development and function.
Subject(s)
Cell Differentiation/immunology , Ephrin-B1/immunology , Immunity, Innate , Interleukin-6/immunology , Lymphocytic Choriomeningitis/immunology , Lymphocytic choriomeningitis virus/immunology , Signal Transduction/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Thymocytes/immunology , Animals , CD8-Positive T-Lymphocytes , Cell Differentiation/genetics , Ephrin-B1/genetics , Interleukin-6/genetics , Lymphocytic Choriomeningitis/genetics , Mice , Mice, Knockout , Organ Size/genetics , Organ Size/immunology , Phosphorylation/genetics , Phosphorylation/immunology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/immunology , Signal Transduction/genetics , Spleen/immunology , Spleen/pathology , Spleen/virology , Th1 Cells/pathology , Th17 Cells/pathology , Thymocytes/pathology , Thymocytes/virology , Thymus Gland/immunology , Thymus Gland/pathology , Thymus Gland/virologyABSTRACT
When total splenectomy is inevitable, heterotopic splenic autotransplantation seems to be the only alternative to maintain the functions of the spleen. The present study was carried out to analyse the critical mass of splenic autotransplant (SAT) for the development of phagocytic activity in rats. Wistar rats were submitted to total splenectomy (TS) alone or in combination with slices of SAT ranging from an average rate of 21·9% (one slice) to 100% (five slices) of the total splenic mass implanted into the greater omentum. Sixteen weeks after the beginning of the experiment, the animals were inoculated intravenously with a suspension of Escherichia coli labelled with Tc-99m. After 20 min, the rats were killed and the liver, lung and spleen or SAT, as well as blood samples were removed to determine the percentage of labelled bacteria uptake in these tissues. As the percentage of the total splenic mass contained in the SAT increased, the bacteria remaining in the blood decreased. From the implant of 26% up to the implant of the total splenic mass (100%) there was no difference in the bacteria remaining in the blood between the healthy animals of the control group and those submitted to TS combined with SAT. This finding shows that the critical mass needed for the development of phagocytic activity of macrophages in splenic autotransplants in adult rats is 26% of the total splenic mass.
Subject(s)
Macrophages/immunology , Phagocytosis , Spleen/immunology , Spleen/transplantation , Animals , Escherichia coli/immunology , Escherichia coli Infections/immunology , Humans , Macrophages/microbiology , Male , Omentum/immunology , Organ Size/immunology , Rats , Rats, Wistar , Spleen/anatomy & histology , Splenectomy , Transplantation, Autologous/immunologyABSTRACT
Matairesinol is one of the lignan compounds found in a variety of plant foodstuffs. We investigated the immunomodulatory effects of (-)-matairesinol in vivo and ex vivo by using mice. Although we found no significant differences in the IgG, IgA and IgM levels in the serum, the IgE level was strongly suppressed by the uptake of (-)-matairesinol in both intact and ovalbumin-immunized mice. The immunoglobulin produced by lymphocytes from the spleen was not activated by the intake of (-)-matairesinol. However, lymphocytes in such gut-associated lymphatic tissues as Peyer's patches and mesenteric lymph nodes were activated by the administration of (-)-matairesinol.
Subject(s)
Furans/pharmacology , Immunologic Factors/pharmacology , Lignans/pharmacology , Animals , Female , Immunization , Immunoglobulin E/biosynthesis , Immunoglobulin E/blood , Lymph Nodes/cytology , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/metabolism , Mice , Mice, Inbred BALB C , Organ Size/drug effects , Organ Size/immunology , Ovalbumin/immunology , Peyer's Patches/cytology , Spleen/anatomy & histology , Spleen/drug effects , Spleen/immunologyABSTRACT
Using ELISA, we have quantified the levels of IL-2 and IFN-gamma in the oral mucosa, ear skin and regional and distant lymph nodes in an experimental murine model of contact sensitivity (CS), induced by the hapten oxazolone (OXA). Compared to normal conditions, the levels of IL-2 peaked early (4-6 h) after hapten exposure in the hapten-exposed tissues analysed both during the first hapten exposure (sensitization) and the second (elicitation) phase, thereafter quickly to subside. The oral mucosa displayed maximal 24-fold increase in IL-2 levels after sensitization and 39-fold increase after elicitation. Respective figures for ear skin were x27 and x35 and for regional lymph nodes x8 and x9, respectively. The distant lymph nodes displayed only minor cytokine increases at any time. IFN-gamma-levels did not increase after sensitization with OXA. An increase in IFN-gamma was seen after the second exposure, peaking at 8-24 h, thereafter quickly subsiding. The oral mucosa IFN-gamma increased x14 after elicitation, the ear skin x8 and regional lymph nodes x37. The weight of the four regional lymph nodes increased from 10 to 38 mg, and the total number of cells in these lymph nodes was increased x11, peaking 48 h after the elicitation. We conclude that in CS reactions, tissue levels of IL-2 increased in buccal mucosa, ear skin and in regional lymph nodes after hapten exposure and re-exposure, IFN-gamma appeared only after re-exposure to the hapten. The increased weight of the regional lymph nodes was mainly attributed to cell proliferation. The common ectodermal origin and the similarity of the CS reactions on skin and in buccal mucosa indicate that these tissues share common immunological patterns of Th1 cell reactivity, at least in dealing with haptens like OXA.
Subject(s)
Dermatitis, Contact/immunology , Interferon-gamma/immunology , Interleukin-2/immunology , Lymph Nodes/immunology , Mouth Mucosa/immunology , Skin/immunology , Animals , Enzyme-Linked Immunosorbent Assay , Female , Kinetics , Male , Mice , Mice, Inbred C3H , Organ Size/immunology , Oxazolone/immunologyABSTRACT
IL-23 stimulates the differentiation and function of the Th17 subset of CD4(+) T cells and plays a critical role in chronic inflammation. The IL-23 receptor-encoding gene is also an inflammatory disease susceptibility gene. IL-23 shares a common subunit with IL-12, a T cell-dependent osteoclast formation inhibitor, and we found that IL-23 also dose-dependently inhibited osteoclastogenesis in a CD4(+) T lymphocyte-dependent manner. When sufficiently enriched, gammadelta T cells also mediated IL-23 inhibition. Like IL-12, IL-23 acted synergistically with IL-18 to block osteoclastogenesis but, unlike IL-12, IL-23 action depended on T cell GM-CSF production. IL-23 did not mediate IL-12 action although IL-12 induced its expression. Male mice lacking IL-23 (IL-23p19(-/-)) had approximately 30% lower bone mineral density and tibial trabecular bone mass (bone volume (BV)/total volume (TV)) than wild-type littermates at 12 wk and 40% lower BV/TV at 26 wk of age; male heterozygotes also had lower bone mass. Female IL-23p19(-/-) mice also had reduced BV/TV. IL-23p19(-/-) mice had no detectable osteoclast defect in trabecular bone but IL-23p19(-/-) had thinner growth plate hypertrophic and primary spongiosa zones (and, in females, less cartilage remnants) compared with wild type. This suggests increased osteoclast action at and below the growth plate, leading to reduced amounts of mature trabecular bone. Thus, IL-23 inhibits osteoclast formation indirectly via T cells in vitro. Under nonpathological conditions (unlike inflammatory conditions), IL-23 favors higher bone mass in long bones by limiting resorption of immature bone forming below the growth plate.
Subject(s)
Bone Density/immunology , CD4-Positive T-Lymphocytes/immunology , Interleukin-18/immunology , Interleukin-23 Subunit p19/immunology , Osteoclasts/immunology , Tibia/immunology , Animals , Bone Density/genetics , CD4-Positive T-Lymphocytes/pathology , Chronic Disease , Dose-Response Relationship, Immunologic , Female , Genetic Predisposition to Disease , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Inflammation/genetics , Inflammation/immunology , Inflammation/pathology , Interleukin-12/genetics , Interleukin-12/immunology , Interleukin-18/agonists , Interleukin-18/genetics , Interleukin-23 Subunit p19/agonists , Interleukin-23 Subunit p19/genetics , Male , Mice , Mice, Knockout , Organ Size/genetics , Organ Size/immunology , Osteoclasts/pathology , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/immunology , Tibia/pathologyABSTRACT
In rats selected for aggressive or domesticated (tame) behavior, spleen morpho-functional changes were examined under the conditions of cell-mediated immune response using experimental autoimmune encephalomyelitis (EAE) model. Tame rats were found to present more severe clinical manifestations, characteristic to EAE, than those with an aggressive behavior. Body mass changes in EAE were significantly different in tame and aggressive rats. The relative adrenal gland mass of control animals in both groups was not different, while in EAE it increased in aggressive rats and remained unchanged in tame rats. The relative spleen mass in control tame rats was greater than in aggressive ones. In EAE, it sharply increased in tame rats and slightly decreased in aggressive animals. Spleen lymphoid nodule diameter in control aggressive rats was smaller than in tame rats. In EAE, it decreased in aggressive rats and remained unchanged in tame rats. In aggressive rats with EAE, marginal zone width decreased more abruptly, while germinal center diameter increased more markedly than in tame animals. It is suggested that different responses to EAE of rats with dissimilar behavioral characteristics, are associated with differently directed effect of their hypothalamic-pituitary-adrenal systems on the balance of cell-mediated and humoral components of the immune response in animals with contrasting behavior.
Subject(s)
Aggression , Behavior, Animal , Encephalomyelitis, Autoimmune, Experimental , Immunity, Cellular , Spleen , Animals , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Organ Size/immunology , Rats , Spleen/immunology , Spleen/pathologyABSTRACT
Castration reduces aggressive and sexual behaviour and provides better carcass quality in bull calves. Vaccination against gonadotrophin-releasing hormone (GnRH) is used as an alternative to surgical castration for the purposes of reducing pain and distress in the animals. Currently, no anti-GnRH vaccine has been authorized for use in cattle in the European Union. The aim of the present study was to assess the effect of an anti-GnRH swine-specific vaccine (Improvac®, Zoetis, USA) on the morphology, structure and function of bull testes. Animals were vaccinated at days 1, 21 and 104 of the experimental period and were classified based on their live weight into the following two groups: LIGHT (172.9⯱â¯30.00â¯kg) and HEAVY (323.8⯱â¯37.79â¯kg). The scrotal circumference was measured on day 1 and prior to slaughter (day 164). At slaughter, the sperm motility and concentration in the caudae epididymis were assessed. Testes were weighed, measured and examined using ultrasound, and then tissue samples were collected and fixed in formalin. Histological and immunohistochemical studies were performed on the testes to measure the diameter of the seminiferous tubules and assess the testicular cell populations. The results revealed that suppression of testicular development was associated with the use of the Improvac® vaccine, which resulted in a smaller size of the testes and impaired spermatid production. However, the effect of Improvac® was more pronounced and consistent in calves vaccinated at a low live weight than at a heavy live weight, which suggested that vaccination is more effective when calves are vaccinated before or early during puberty. However, testes from calves vaccinated at a low live weight were more prone to the development of intraluminal concretions in the seminiferous tubules.
Subject(s)
Gonadotropin-Releasing Hormone/immunology , Orchiectomy/methods , Testis/anatomy & histology , Vaccines, Contraceptive/immunology , Animals , Cattle , Male , Organ Size/immunology , Scrotum/anatomy & histology , Spermatozoa/physiology , VaccinationABSTRACT
Following hematopoietic stem cell transplantation (HSCT), thymic reconstitution of peripheral T lymphocytes is essential to avoid a chronically immunodeficient state and disease recurrence. The purpose of this study was to determine if children and adolescents with treatment refractory SSc, awaiting HSCT, have sufficient thymic function to reconstitute T lymphocyte function after transplantation. Thirteen children with systemic scleroderma were enrolled and assessed by physical exam, chest MRI, measurement of autoantibodies, B and T cell immuno-phenotyping, and quantization of T cell receptor rearrangement excision circles (TREC) as a marker of thymopoiesis. MRI detected thymic tissue in 9/13 children. TREC levels were detectable in all but one child but were significantly reduced (p<0.001) when compared to a control population. SSc patients also had a reduced percentage of naïve (CD45RA+CD31+) CD4+ T lymphocytes, further indicating diminished thymopoiesis. Our data suggest that thymic function in children with SSc might be insufficient for an adequate immunoreconstitution following transplantation in some patients. A thorough evaluation of immune and thymic functions to identify those patients prior to HSCT is recommended.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Receptors, Antigen, T-Cell/immunology , Scleroderma, Systemic/immunology , T-Lymphocyte Subsets/immunology , Thymus Gland/immunology , Adolescent , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Cell Proliferation , Child , Female , Humans , Leukocyte Common Antigens/blood , Leukocyte Common Antigens/immunology , Linear Models , Magnetic Resonance Imaging , Male , Organ Size/immunology , Scleroderma, Systemic/therapy , Thymus Gland/anatomy & histology , Young AdultABSTRACT
OBJECTIVE: Hepatic venoconstriction plays a significant role in anaphylactic hypotension in anesthetized rats. The purpose of this study is to determine whether the primary site of anaphylactic venoconstriction in the liver venous circulation occurs prior to or distal to the sinusoidal capillaries. We also determined whether the hepatic blood volume is increased during anaphylactic hypotension. METHODS: We measured, using a servo-null micropipette pressure-measuring system, the hepatic venular transmural pressure (P micro hv) at the liver surface of anesthetized rats sensitized with the antigen of ovalbumin (1 mg). We also measured the liver lobe thickness, using the ultrasonic crystal dimension measuring system. Anaphylactic hypotension was induced by an intravenous injection of 0.6 mg ovalbumin. RESULTS: When the antigen was injected, the systemic arterial pressure decreased profoundly from 118+/-9 to 45+/-4 mm Hg, which was accompanied by an increase in Ppv and P micro hv: P micro hv only transiently increased from 3.1+/-0.9 to 8.8+/-1.5 cm H(2)O at 1 min and then rapidly returned to the baseline within 2 min, when Ppv continued to increase and reached the peak of 36+/-7 cm H(2)O at 3.5 min after antigen. This greater increase in Ppv-to-P micro hv gradient than that in P micro hv-to-Pcv gradient after antigen indicated that the constriction of the portal veins and the sinusoids much predominates over that of the hepatic veins. Along with this hepatic pre- and sinusoidal constriction, the liver lobe thickness significantly decreased by 4% after antigen. CONCLUSION: Pre-sinusoidal constriction during anaphylactic shock in anaesthetized rats increased the portal venous pressure while the hepatic venular pressure only increased slightly and transiently. This predominant pre-sinusoidal constriction is accompanied by a decrease in liver volume.
Subject(s)
Anaphylaxis/physiopathology , Blood Pressure/physiology , Hypotension/physiopathology , Liver/blood supply , Anaphylaxis/chemically induced , Anaphylaxis/immunology , Anesthesia , Animals , Antigens/adverse effects , Antigens/immunology , Blood Volume/drug effects , Hepatic Veins/drug effects , Hepatic Veins/immunology , Hypotension/chemically induced , Hypotension/immunology , Liver/drug effects , Liver/immunology , Liver Circulation/drug effects , Liver Circulation/immunology , Male , Organ Size/drug effects , Organ Size/immunology , Ovalbumin/immunology , Ovalbumin/pharmacology , Portal Pressure/drug effects , Portal Vein/drug effects , Portal Vein/immunology , Rats , Rats, Sprague-Dawley , Time Factors , Vasoconstriction/drug effects , Vasoconstriction/immunology , Veins/drug effects , Veins/immunology , Venous Pressure/drug effectsABSTRACT
Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.