Bone-derived MSCs encapsulated in alginate hydrogel prevent collagen-induced arthritis in mice through the activation of adenosine A2A/2B receptors in tolerogenic dendritic cells

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Reflections on Relationship Between Pathogenesis of Endometriosis and Intestinal Flora / 中国实验方剂学杂志

Endometriosis is a multiple disease that afflicts the health of women at childbearing age,and its incidence rate has been increasing year by year,furthermore,there has been a trend to be younger.At present,the pathogenesis of endometriosis has been not expounded completely,its cure rate is not high with high recurrence rate.In recent years,studies have shown that the human is a commensal body composed of a large number of microorganisms,and especially the microorganisms in the intestinal are closely related to the health of the body.Based on the previous studies on endometriosis,this paper proposes that its pathogenesis may be related to intestinal microbiological disorder,and aims to provide new ideas for the treatment of endometriosis.

Inmunotolerancia en un paciente hemofílico pediátrico en Costa Rica / Immunotolerance induction in a pediatric hemophilic patient in Costa Rica

Resumen La hemofilia A es una enfermedad ligada al cromosoma X que predispone al sangrado. Se trata con Factor VIII, ya sea profilaxis o a demanda. La mayoría de países en el resto del mundo utilizan profilaxis, lo cual a la larga es más barato que tratar los pacientes cuando están con un sangrado activo. La producción de inhibidores del factor VIII es la complicación más común y seria del tratamiento. La inmunotolerancia (ITI) es la única opción de tratamiento que ha demostrado satisfactoriamente erradicar esta condición en los pacientes que desarrollan inhibidores, disminuyendo de esta manera no solo los inhibidores sino los costos del tratamiento. Se presenta un caso de inducción satisfactoria de inmunotolerancia con bajas dosis de factor VIII (FVIII) en un paciente pediátrico con hemofilia A severa. A pesar de que la inmunotolerancia se ha practicado antes en Costa Rica, un caso de estos nunca antes había sido publicado.

Abstract Hemophilia A is an X - linked bleeding disorder. It can be treated with Factor VIII prophylaxis or on demand treatment. Most countries in the world use prophylaxis as it is less expensive than treating patients when they are bleeding. The production of factor VIII inhibitors is the most common and serious complication of the treatment. Immune tolerance induction (ITI) is the only option of treatment when patients develop inhibitors proven to be successful to eradicate this condition, therefore decreasing inhibitors and costs. A case of a successful immune tolerance induction with low doses of factor VIII (FVIII) in a pediatric patient with severe hemophilia A and FVIII inhibitors is presented. Even though inmunotolerance has been practice before in our country, a case like this has never been published.

Comportamiento de las células asesinas naturales, las dendríticas y los macrófagos, en el embarazo / Behavior of the natural killer cells, dendritic cells and macrophages in pregnancy

La implantación de un embrión semialogénico en el útero materno constituye una paradoja inmunológica y es uno de los fenómenos que abre más interrogantes dentro del campo de la Inmunología. Mientras que en un determinado momento se consideró que la interfase materno-fetal era un sitio inmunológicamente privilegiado, hoy se sabe que ocurre un reconocimiento del feto semialogénico por el sistema inmune de la madre. Sin embargo, a pesar de este reconocimiento inmunológico se han descubierto varios mecanismos que pueden explicar el porqué la madre no rechaza al feto antigénicamente diferente. Estos mecanismos incluyen, tanto factores fetales como factores locales maternos, donde están incluidos los elementos de la respuesta inmunitaria adaptativa e innata. En este trabajo se hace referencia a la importante función que desempeñan las células asesinas naturales, las células dendríticas y los macrófagos en el embarazo(AU)

The implantation of a semiallogenic embryo in the womb is an immunological paradox and is one of the phenomena that open more questions in the field of immunology. While at one point it was considered that the maternal-fetal interface was an immunologically privileged site, now it is known that a fetus semiallogenic recognition by the immune system of the mother occurs. However, despite this immune recognition several mechanisms have been discovered that may explain why the mother does not reject the fetus antigenically different. These mechanisms include both fetal factors and local maternal factors, where the elements of innate and adaptive immune response are included. In this paper we refer to the important role of natural killer cells, dendritic cells and macrophages in pregnancy(AU)

Study of effect and molecule mechanism of Shou Tai Decoction on URSA treatment by regulating function of dendritic cells / 中国免疫学杂志

Objective:To investigate the role of dendritic cells(DC) in unexplained recurrent spontaneous abortion(URSA) and to study the effect and molecular mechanism of Traditional Chinese Medicine Shou Tai Decoction ( STD ) on URSA treatment by regulating the function of DC.Methods:30 cases of normal pregnancy women and 30 cases of URSA patients were taken as control group and URSA group respectively.URSA patients were treated with Shou Tai Decoction.Peripheral blood mononuclear cells were taken from both control group and URSA group before and after STD administration.The proportion of CD11c+HLA-DR+cells,CD11c+CD80+cells and CD11c+CD86+cells in peripheral blood were measured by flow cytometry.Moreover,the mRNA expression of HLA-DR,CD80,CD86 and Indoleamine2,3-dioxygenase( IDO) in venous blood were detected by RT-PCR assay.The protein expression of IDO was detected by Western blot.Furthermore, the cytokines, including IL-12p70 and IL-6, in the blood serum were measured by ELISA.Results:Compared with normal pregnancy women,the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 of URSA patients in peripheral blood were both increased significantly(P<0.05), while the mRNA and protein expression of IDO were decreased markedly(P<0.05).Additionally,the level of IL-12p70 and IL-6 in serum of URSA women were significantly increased ( P<0.01 ) .When compared with URSA patients before STD administration, the proportion of CD11c+HLA-DR+,CD11c+CD80+,CD11c+CD86+cells and the mRNA expression of HLA-DR,CD80,CD86 decreased significantly after STD administration ( P<0.05 ) , while the mRNA and protein expression of IDO increased markedly after STD administration(P<0.05).Meanwhile,compared with before STD administration,serum protein level of IL-12p70 and IL-6 of URSA patients decreased significantly after STD treatment ( P<0.01 ) .Conclusion: The changes of proportion and function of DC were involved in URSA.The regulatory effect of STD on DC proportion and function contribute to the treatment of URSA.

Unusual outcome of in utero infection and subsequent postnatal super-infection with different PCV2b strains / 中国病毒学·英文版

VC2002, isolated from postweaning multisystemic wasting syndrome (PMWS)-affected pig, is a mixture of two porcine circovirus genotype 2b (PCV2b) viruses, K2 and K39. Preliminary experiments disclosed short-term adverse effects of K39, but not K2, on porcine foetuses. These findings led to the hypothesis that infection of immuno-incompetent foetuses with K2 confers a status of immunotolerance, and postnatal super-infection with K39 triggers PMWS. To explore this hypothesis, nine 55-day-old foetuses were inoculated in utero (three with K2-104.3TCID50, three with K39-104.3TCID50 and three with medium), and foeto-pathogenicity examined. At 21 days post-inoculation (dpi), K2 did not induce pathology, whereas pathological effects of K39 were evident. Twenty-four 45-day-old foetuses were subsequently inoculated to examine the long-term effect of K2, including six with K2-high dose-104.3TCID50, six with K2-low dose-102.3TCID50 and 12 mock-inoculated controls. Both doses resulted in ifve mummiifed foetuses and one live-born piglet each (69dpi). K2 was recovered from all mummies. K2 and K2-speciifc antibodies were not detected in serum of the two live-born piglets at birth, indicating full control of K2 infection. The K2-low dose-infected piglet was immunostimulated at day 2, but not the K2-high dose-infected piglet. Both non-stimulated and stimulated K2-infected piglets were super-inoculated with K39 at day 6 or 8 (taken as 0 days post super-inoculation). Low viral replication was observed in the non-stimulated K2-K39 piglet (up to 103.3 TCID50/g;identiifed as K39). In contrast, viral replication was extremely high in the stimulated K2-K39 piglet (up to 105.6TCID50/g) and identiifed as K2, indicating that K2 infection is controlled during foetal life, but emerges after birth upon immunostimulation. However, none of the piglets showed any signs of PMWS.

Study on induction of immunotolerance against Graves' disease in neonatal mice / 中华内分泌代谢杂志

Objective To investigate the feasibility of inducing neonatal immunotolerance against Graves'disease by gene TSH receptor (TSHR) 289 and its possible mechanism.Methods Neonatal (0-24 h) female BALB/c mice were divided into intraperitoneal injection group,intramuscular injection group,model group,and normal control group.The intraperitoneal group and the intramuscular group were further divided into low-dosage,middle-dosage,high-dosage tolerance groups,and the coresponding control groups.The tolerance groups and the controls were intraperitoneally or intramuscularly pretreated with low-dosage( 1×106 particles),middle-dosage( 1 × 108particles),high-dosage( 1 × 1010 particles)of Ad-TSHR 289 or Ad-lacz respectively.6 to 7 weeks later,the normal control group received intramuscular injection with Ad-lacz; the other groups were immunized with Ad-TSHR289,three times at 3 weeks interval.10 days after the first immunization,serum TRAb was detected.4 weeks after the last immunization,serum TRAb,TT4,splenic CD4 + CD25 + Foxp3/CD4 + were tested,and the thyroid tissues were examinated histologically.Results Ten days after the first immunization,no antibody response against TSHR was detected in the two high-dose tolerance groups,but the TRAb titer in respective controls was significantly higher( P＜0.05 ).4 weeks after the last injection,in high-dose tolerance groups,only 1/10 of mice immunized by intraperitoneal or intramuscular injection elicited anti-TSHR antibody,and no mice immunized intraperitoneally had elevated serum TT4.Two of ten mice challenged intramuscularly showed slightly increased TT4 levels,but the respective controls displayed a strong antibody response( P＜0.01 ) and elevated TT4 level ( P＜0.05 ).The similar percentages of high TT4 and thyroid hyperplasia were found in all groups.Additionally,the frequencies of CD4+CD25 +Foxp3/CD4+in two high-dose tolerance groups were significantly increased as compared to those in controls( P＜0.05 ).The incidence of Graves' disease in the other groups by intraperitoneal or intranuscular injections was not statistically different from those in the corresponding control groups and the model group.Conclusions The immune tolerance against Graves'disease is induced in neonatal mice by either intraperitoneal or intramuscular pathway with specific antigen of TSHR 289,carried by adenovirus vector,and then inhibits Graves' disease in adults. Stimulation with the high-dosage antigen is liable to induce immune unresponsiveness.CD4 + CD25 + Foxp3 +T cells may play an important role in the induction and maintenance of tolerance.

Effect of agonist CD40 monoclonal antibody on the tolerance of experimental autoimmune myasthenia gravis / 中华神经医学杂志

Objective To investigate the effect of agonist CD40 monoclonal antibody (CD40mAb) on the tolerance of experimental autoimmune myasthenia gravis (EAMG) induced by immature dendritic cells (iDCs). Methods Lewis rats were equally randomized into normal group,EAMG group, tolerance group and CD40mAb treatment group (n=5). Rats in the tolerance group and CD40mAb treatment group were vaccinated with AChR pulsed iDCs; and rats in the CD40mAb treatment group were intraperitoneally injected CD40mAb at a dosage of 0.5 mg once when performing the vaccination and on the 2rd d of vaccination. One mL serum-free medium was given to the rats in the EAMG group; normal group did not receive any treatment. Three weeks after that, rats in the above 4 groups were immunized with AChR and complete Freund's adjuvant (CFA). Seven weeks after the immunization, the corresponding indexes of MG were observed: behavioral assessment was performed and electromyogram was employed to detect the repetitive nerve stimulation on these rats; enzyme-linked immunosorbent assay (ELISA) was used to determine the level of AChRab; the pathological changes of neuromuscular junction were also detected. Results Just as the rats in the normal group, the rats in the tolerance group did not have significant changes in any of the corresponding indexes of MG after being immunized with AChR and CFA. In contrast, rats in both EAMG group and CD40mAb treatment group showed typical changes in the corresponding indexes of MG: their electromyogram wave amplitude obviously attenuated; the level of serum AChRab increased and neuromuscular junction appeared as a typical damage of MG. Conclusion Agonist CD40mAb could abrogate the tolerance of EAMG induced by AChR pulsed iDCs, suggesting that the dysfunction of DCs is related to the priming of abnormal immune of MG.

Organ allografts combined with hematopoietic stem cell transplantation and immunotolerance / 中华肝胆外科杂志

Our understanding of the immunological mechanisms of rejection has greatly improved over the past 10 years. The allografts have maintained long survival without immunosuppressive treatment in the several organ-transplant recipients combined with hematopoietic stem cell transplantation. The authors attributed the successful outcome to the cotransplantation of donor stem cells. The review will analyze firstly conditions of the recipients, and then review the theoretical basis and history regarding donor-specific tolerance of allograft, and it will also clarify that there is no direct link between the donor-specific transplantation tolerance and hematopoietic stem cell transplantation.

Role and mechanism of human Kupffer cells in liver allo-geneic transplantation / 中华肝胆外科杂志

Objective To explore the possible role and mechanism of the Kupffer cells (KCs) in liver allo-geneic transplantation at the early stage. Methods In vitro cell contact coculture system was established. Culture supernatants were collected respectively on the 1st, 2nd, 4th, 6th d after cocul-ture and the KCs and PBMCs were harvested on the 6th day after culture. The expression of HLA-G on the membrane of the KCs and PBMCs was detected with immunochemistry. Nitrate reduction test was used to determine the concentration of nitric oxide. IFN-γ, IL-10, TGF-β1 cytokine levels in the supernatants were also measured with ELISA. The proliferation of lymphocytes was evaluated with MTT. Results six days later, no HLA-G molecules were detected on the membrane of the KCs and PBMCs. In the experimental group containing KCs, the levels of NO, IL-10 and TGF-β1 was signifi-cantly increased(P<0. 05), while the levels of IFN-γ was relatively lower(P<0. 05) as compared to the experimental group without KCs. No IL-10 and IFN-γ were detected in the control group, and on-ly few NO and TGF-β1 was found in the control group with KCs. MTT test showed that the value of optical density was lower in the experimental group with KCs than that in any other group(P<0. 05).Conclusion No HLA-G is expressed on the membrane of KCs and PBMCs after contact coculture.KCs may participate in regulating production of NO and Th2/Th3-like cytokines and suppressing the proliferation of lymphocytes, through which KCs probably take part in inducing immunotolerance of liver transplantation in early stage.

The Expression of Indoleamine-2,3-dioxygenase in Non-small-cell Lung Cancer / 华中科技大学学报(医学版)

Objective To study the expression and significance of indoleamine-2,3-dioxygenase(IDO)in non-small-cell lung cancer(NSCLC).Methods Thirty-eight cases of lung cancer tissues and 10 cases of paracancerous normal lung tissue were collected.The semiquantitative immunohistochemistry was used to detect the positive rate of IDO and fluorescent quantitative PCR to detect the level of IDO mRNA in the lung tissues respectively.Results The positive rate of IDO and the level of IDO mRNA in NSCLC group were significantly higher than in paracancerous normal lung tissues(P＜0.05).There was no significant difference in the positive rate of IDO and the level of IDO mRNA between the adenocarcinoma group and the squamous cell carcinoma group(P＞0.05).Statistically,there was significant difference in positive rate of IDO and the level of IDO mRNA among low,middle and high differentiation groups(P＜0.05).There was significant difference in positive rate of IDO and the level of IDO mRNA between the lymph node metastasis and non-metastasis groups(P＜0.05).Conclusion The high expression of IDO in NSCLC is correlated with the degree of differentiation and the metastasis of lymph nodes,but not with the pathological types.

The frequency and function of FoxP3~+ regulatory T cell in patients with acute hepatitis B / 细胞与分子免疫学杂志

AIM: To investigate the dynamic variety of frequency and function of FoxP3~+ regulatory T cells in patients with acute hepatitis B (AHB). METHODS: Peripheral blood mononuclear cells (PBMCs) from 15 AHB patients at acute phase (week 1 of illness), convalescent phase (primary occurrence of both ALT level normalization and HBsAg negative conversion), resolved phase (at least 8 weeks after both ALT normalization and HBsAg seroconversion, and 15 health subjects were analyzed for FoxP3 (Forkhead/winged helix transcription factor) mRNA expression in MACS magnetic beads-purified CD4~+ T cells by real-time RT-PCR assay. The effects of Treg cells on the proliferation of CD4~+CD25~- T cells were examined by a ~3[H]-thymidine incorporation assay. RESULTS: AHB patients presented a significantly higher FoxP3 mRNA expression at convalescent phase than acute phase (t=-6.04, P<0.01) and resolved phase (t=4.45, P<0.01), and healthy controls (t=3.44, P<0.01). We also observed that the suppression efficiency of Treg cells on proliferation of CD4~+CD25~- T cells was lower at acute phase than convalescent phase (t=-5.30, P<0.01) and resolved phase (t=-3.20, P<0.05), but there was no significant difference between healthy controls and any phase of AHB. CONCLUSION: AHB patients presented lower circulating Treg frequency and suppression function at acute phase, and both of them are increased at convalescent phase, and then return to normal level along with disease resolved. This follow-up study furthers our understanding of Treg' s role in immunopathogenesis of hepatitis B.

Duction of immunoincompetence of T cells to oxidized-low density lipoprotein in vitro by CTLA4Ig / 中华微生物学和免疫学杂志

Objective To induce the immunoincompetence of T cells to oxidized-low density lipoprotein(ox-LDL)in vitro,in order to prevent immune injuries in atherosclerosis(AS)and to find new strategies to prevent AS.Methods Monocytes were separated from peripheral blood to induce dendritic cells (DC).DCs were treated with LPS(30 ng/m1),ox-LDL(10μg/m1)and LDL(10μg/m1)for 48 h,respectively.Then DCs were mixed with allogeneic T lymphocytes to earry out mixed lymphoeytes reaction (MLR).CTLA4Ig in different concentrations was added into the MLR of ox-LDL group.MTr method was used to assay the proliferation of T cells.The CD25 expression and apoptosis of T cells in MLR were tested by flow cytometry.And the excretion of IL-2,IFN-γ and IL-4 were assayed by ELISPOT method.Results SI of the ox-LDL group was higher than that of the LDL group significantly(DC:T=1:5,1.6717±0.3152vs 1.4250±0.2874.P<0.05;DC:T=1:10,1.5458±0.2748 vs 1.3352±0.2991,P<0.05),and CTLA4Ig inhibited the SI of the ox-LDL group in dose-dependence(CTLA4Ig 1.25μg/ml,0.96±0.30 vs μg/ml 1.29±0.28 vs 1.64±0.33 P<0.05).CTLA4Ig caused the decrease of CD25 expression(CTLA4Ig 1.25 μg/ml,11.26±0.58 vs 14.25±1.02,P<0.05;CTLA4Ig 10μg/rnl 8.42±0.45,P<0.01)and induced apoptosis of T cells in MLR(CTLA4Ig 1.25μg/ml,12.54±3.69 vs 6.09 4-2.24,P<0.05;CTLA4Ig 10μg/ml,26.87±5.06 VS 6.09±2.24,P<0.01).CTLA4Ig caused the decrease of ELISPOT counts of IL-2(CTLA4Ig 1.25μg/ml,386±42 VS 534±54,P<0.05;CTLA4Ig 10μg/rnl,230±27 VS 534±54,P<0.01)and IFN-γ(CTLA4Ig 1.25μg/ml,445±48 VS 672±46,P<0.05;CTLA4Ig 10μg/ml,193±39 VS 672±46,P<0.01),while that of IL-4 increased(CTLA4Ig 1.25μg/ml,401±32 VS 332±41,P<0.05;CTLA4Ig 10μg/ml,453±57 VS 332±41,P<0.05).Conclusion CTLA4Ig can induce T cens immunoin competence to ox-LDL in vitro by inhibiting T cells activation,inducing T cells apoptosis and TH 1/TH2 immune deviation.

The test of fas ligand gene transfection on inducing renal transplant immunotolerance in rats / 重庆医科大学学报

Objective:To investigate the effect of Fas ligand(FasL) gene transfection to renal allograft in rats. Methods: Firstly Establish renal transplantation model of rat. Secondly FasL recombinant adenovirus vector was contruccted and transduced into rat renal allografts by renal artery perfusion.Immunohistochemistry were used to detect the expression of exogenous FasI gene. Electronic microscopy was used to observe the changes in the ultrastructure.At the same time,mean survival of animals and the level of serum creatinine were observed.Results:Through animal experiment,we found: the mean survival time was 31.3 days in Ad-FasL treated group, whereas the the mean survival time of without treatment group was 9.1 days. The mean survival time increased 22 days in Ad-FasL treated group.There has significant difference. Conclusions:Adenoviral vector can successfully transfection rat kidneys with the FasL cDNA. FasL gene transfection can protect rat renal allografts from immunologic attack and prolong the allograft surviva1.

Experimental Study on Induction of Tolerance to Experimental Autoimmune Myasthenia Gravis by Immature Dendritic Cells / 华中科技大学学报（医学）（英德文版）

To investigate the effect of immature dendritic cells (iDCs) on experimental autoimmune myasthenia gravis (MG), iDCs were generated in low dose of GM-CSF, and then they were pulsed with acetylcholine receptor (AchR) and transferred to allogeneic rats. After 3 weeks, all rats were immunized with AchR and complete Freund's adjuvant (CFA) and observed for the corresponding indices of MG for 7 weeks. Our results showed that compared with mature DCs (mDCs) generated at high dose of GM-CSF plus additional stimulation by lipopolysaccharide, iDCs expressed significantly lower levels of MHC-Ⅱ , CD80 and CD86, and their ability to uptake FITC-Dextran was stronger but the ability of stimulating proliferation of allogeneic T cells were weaker. Like controls,after immunization, all rats transferred with iDCs, mDCs and AchR-pulsed mDCs showed typical symptoms in 4 to 7 weeks. The amplitude of electromyogram wave dropped obviously, the level of serum AchRab increased and neuromuscular junction showed typical damage of MG. In contrast, no conspicuous changes were noted in rats transferred with AchR-pulsed iDCs. The results suggest that iDCs could be generated by inducing bone marrow precursors in low dose of GM-CSF, AchRpulsed iDCs could induce tolerance of EAMG. The dysfunction of DCs may play an important role in the initiation and maintenance of normal immune response in MG.

Studies on the prolongation of cardiac allograft survival by alloreactive lymphocytes depletion. indaection of allograft immunotolerance by alloreactive lymphocyte vaccine in recipient preparation / 临床外科杂志

Objective Alloreactive lymphocytes specific for graft antigens are implicated in rejection of allograft.This study aims to induce alloreactive lymphocytes depletion or inactivation and allograft immuno tolerance by alloreactive lymphocyte vaccine(ALV).Methods Recipient lymphocytes were expanded for 9-14 days stimulated by donor lymphocytes that had been dealt with mitomycin C.The expanded recipient lymphocytes are termed alloreactive lymphocyte vaccine(ALV).About 0.5?10 7～1.0?10 7cells mixed with freunds complete ajuvant(FCA)were used as ALV to vaccinate itself for 3～4 times as usual. The stimulate index(SI) was measured after vaccination and compared with itself unvaccination. Results The ALV could suppress mixed lymphocyte reaction. The stimulate Index was significantly lower than themselves uninjected with ALV(P

Intrathymic inoculation of liver specific antigen protects hepatocytes from apoptosis after liver allotransplantation / 中国病理生理杂志

AIM: To study the effects of intrathymic inoculation of liver specific antigen (LSA) on hepatocyte apoptosis after liver allotransplantation. METHODS: Orthotopic liver transplantation was used in this study. Group Ⅰ: syngenic control (Wistar-to-Wistar); Group Ⅱ: acute rejection (SD-to-Wistar); Group Ⅲ: thymus inoculation of SD rat LSA day 7 before transplantation. The observation of general situation and survival time, hepatocyte apoptosis and LAT expression in liver transplants were used to analyze immune state of animals in different groups. RESULTS: The general situation of group Ⅰ was very well after transplantation. Recipients of groupⅡ lost body weight progressively and all died within day 9 to day 13 post transplantation. As for group Ⅲ, the general situation of recipients was remarkably better than that in group Ⅱ. The positive cells of apoptosis in group Ⅲ detected by TUNEL were not significantly different from that in group Ⅰ, but was significantly lower than that in group Ⅱ. LAT was detected at any time in group Ⅱ with peak expression at day 5 and day 7 post transplantation. In contrast, LAT was not detected in any other groups. CONCLUSION: Intrathymic inoculation of LSA protects hepatocytes from apoptosis after liver allotransplantation.

Study of inducing immunotolerance by intrathymical injection allogenic H-2 antigen / 中国免疫学杂志

Objective:To study the effects of intrathymical injection allogenic antigen on the establishment of donor specific transplantation immunotolerance.Methods:H 2 antigen extracted from splenic cells of donor C56BL/6 mice was intrathymically injected to recipients adult Balb/c mice, one week later,donor C57BL/6 or C3H skingrafts were transplanted,observing transplanted skin survival times ,meanwhile MLC?CML ?DTH was detected.Results:the median survival time (MST) of transplanted skin allografts was over 70 days in tolerance recipients while the skin MST graft in the control group was 12.6?1.69 days,tolerance recipients normally rejected the donor C3H skin grafts (MST 13.4 ? 1.42 days), MLC detection showed that tolerance recipient splenocyte responded to C57BL/6 stimulator significant reduction ,but in normal reaction to donor C3H stimulator,the CML and DTH of tolerance recipient splenocyte to target cell of donor C57BL/6 was inhabited.The results suggested that slpecific tolerance might be induced by intrathymic injection. Conclusion:The intrathymic injection of donor H 2 antigen extracted from C57BL/6 splenic cells could induce recipients specific tolerance to skin transplantation.

Study on the immunological function of sodium butyrate-induced immature human monocyte-derived dendritic cells / 中国病理生理杂志

AIM: To investigate the immunological function of sodium butyrate-induced immature dendritic cells in vitro.METHODS: The human monocyte-derived dendritic cells were induced in the presence of human granulocyte macrophage-colony stimulating factor(GM-CSF) and interleukin-4 (IL-4), combined with sodium butyrate. The immunological function of sodium butyrate-induced dendritic cells was detected by the FCM, endocytic activity, T cells stimulatory proliferation capacity, and interleukin-12 (IL-12) production.RESULTS: Sodium butyrate could down-regulate the major histocompatibility complex(MHC) class II and costimulatory molecules of dendritic cells, increase the endocytic activity, induce a stage of T-cell anergey, and inhibit the T helper cell type 1-skewing factor IL-12 production. CONCLUSION: Sodium butyrate inhibits the maturation of dendritic cells and induces production of immature dendritic cells, which may help to explore the machenism of its epigenitic modification.

Microchimerism in the cell-free blood samples of recipients associates with the acceptance of transplanted kidneys / 中国免疫学杂志

Objective:To examine whether the existence of the donor-and-recipient-derived DNA chimerism in recipient’s plasma can be a predictive marker for the status of transplanted organ.Methods:One hundred and twenty-six female patients who had been transplanted with male kidney were enrolled in the present study.In these female recipients,the SRY1,DYZ11st and DYZ12nd genes on the Y chromosome from the plasma were prospectively examined using reverse transcription polymerase chain reaction (RT-PCR).Results:SRY1,DYZ11st and DYZ12nd sequences were detected in the cell-free blood (plasma) of 97 (77%) of 126 female patients with male kidney.The average time-span when the transplanted kidneys functioned was 8.7 years and 5.4 years among microchimerism-positive and microchimerism-negative recipients,respectively.The frequency of the patients who had acute rejection after renal transplantation was approximately 10% and 28%in microchimerism-positive and microchimerism-negative recipients,respectively.Serum creatinine levels in microchimerism-positive patients were significantly lower than those in microchimerism-negative patients.Conclusion:These results suggest that plasma DNA microchimerism is present in certain patients following renal transplantation and measurement of plasma DNA microchimerism using quantitative RT-PCR might be a useful predictor for the acceptance of transplanted kidneys.