Evaluation of gravity effect on inferior vena cava and abdominal aortic flow using multi-posture MRI.

BACKGROUND: Inferior vena cava flow (IVCF) and abdominal aortic flow (AAF) are essential components of the systemic circulation. Although postural changes might alter IVCF and AAF by the gravity effect, the exact details are unknown. PURPOSE: To evaluate the effect of gravity on IVCF and AAF using a novel magnetic resonance imaging (MRI) system that can image in any position. MATERIAL AND METHODS: Caval velocity-mapped images were obtained using the cine phase-contrast technique in the upright and supine positions with multi-posture MRI (n = 12). The mean IVCF/AAF velocity, maximum IVCF/AAF velocity, cross-sectional area of IVC/AA, mean IVCF/AAF, maximum IVCF/AAF, and heart rate in the two positions were assessed. RESULTS: The mean IVCF velocity, maximum IVCF velocity, cross-sectional area of IVC, mean IVCF, maximum IVCF, mean AAF velocity, maximum AAF velocity, mean AAF, and maximum AAF were significantly lower in the upright position compared with the supine position (P < 0.05 for all), with differences of 52% ± 33%, 36% ± 19%, 56% ± 18%, 26% ± 18%, 19% ± 11%, 33% ± 13%, 33% ± 22%, 42% ± 21%, and 37% ± 28%, respectively. Heart rate was significantly higher in the upright position compared with the supine position (116% ± 9.2%; P = 0.003). There were no differences in cross-sectional area of AA between the two positions (108% ± 22%; P = 0.583). CONCLUSION: The effect of gravity decreases IVCF and AAF. Clarifying the effect of gravity on IVCF and AAF during a postural change may help to improve the management of patients with circulatory disease.

Passive immunization against inhibin increases testicular blood flow in male goats.

The present study investigated whether or not passive immunization against inhibin modulates testicular blood flow in goats. Male Shiba goats were injected with either 10 ml of inhibin antiserum (INH group; n = 5) or 10 ml of normal castrated goat serum (NGS group; n = 4). Concentrations of FSH, LH, testosterone (T), and estradiol (E2) in the plasma were measured by radioimmunoassay. Blood flow within the supratesticular (STA) and marginal testicular arteries (MTA) were measured by color pulsed-Doppler ultrasonography, and Doppler indices (resistive index; RI and pulsatility index; PI) were recorded. Results revealed significant increases in concentrations of FSH and E2 in the INH group compared to those in the NGS group (P < 0.05). Animals in the INH group had greater (P < 0.05) FSH concentrations than those in the NGS group in the period between 60 h and 144 h after treatment than at any other time. Estradiol concentrations were greater (P < 0.05) in the INH group than in the NGS group at 6 h (12.15 ± 2.09 pg/ml vs 5.49 ± 1.17 pg/mL), 12 h (8.27 ± 1.29 pg/mL vs 3.05 ± 0.38 pg/mL), and 36 h (9.35 ± 1.31 pg/mL vs 5.09 ± 0.46 pg/mL) after treatment than at any other time. Concentrations of LH and T did not significantly change between the two groups. Goats in the INH group had lesser (P < 0.05) RI of the STA than those in the NGS group and RI values were lesser at 24 h (0.37 ± 0.031 vs 0.49 ± 0.004) and 120 h (0.38 ± 0.028 vs 0.55 ± 0.048) after treatment than at any other time. Furthermore, values of RI and PI of the MTA were significantly lesser (P < 0.05) in the INH group compared to those in the control group at 48 h (RI of MTA: 0.21 ± 0.014 vs 0.37 ± 0.039; PI of MTA: 0.24 ± 0.016 vs 0.46 ± 0.058) after treatment than at any other time. In conclusion, passive immunization against inhibin has a stimulatory effect on testicular blood flow in goats by inducing decreases in the RI values of the STA and MTA.

The immune influence of a parabiosis model on tumour-bearing mice.

AIM: The aim of this study was to analyse the immune influence of a parabiosis model on tumour-bearing mice. METHODS: Parabiosis was established between C57BL/6 wild-type mice expressing green fluorescent protein (GFP+) and C57BL/6 wild-type mice without green fluorescent protein (GFP) to ensure blood cross-circulation between animals, and then the expression of CD4+ T cells, CD8+ T cells and interleukins 2, 4 and 10, and interferon-gamma (INF-γ) in spleen cells of parabiosis model mice were examined with flow cytometry. At day 8 and day 14 after conjoined surgery, we were aiming to sample tumour tissue in the parabiosis mice and observe changes of CD3, CD4, CD8, CD31, IFN-γ and vascular endothelial growth factor (VEGF) through immunohistochemical analysis. RESULTS: The interaction of blood was established on the third day with modelling rate of 85.7% after blood interaction. The healthy cells of GFP+ C57 mice entered the blood circulation of tumour-bearing mice via a connecting capillary network, playing a role in stimulating CD4+ and CD8+ cells in the tumour-bearing mice so that CD4+ cells increased more in tumour-bearing mice than in the positive control group (p <0.05). The number of GFP+ cells that were detected in a tumour-bearing mouse was small, but GFP+ cells can stimulate the mouse itself to generate more CD4+/interleukin (IL)-4, CD4+/IL-10 (p <0.05).The numbers of CD4+/IL-2, CD4+/IL-4 and CD4+/IL-10 among the GFP+ mice were higher than those in the negative control group(p <0.05).The levels of IFN-γ in both mice in the parabiosis model were decreased (p <0.05). The rate of CD4+/CD8+ in parabiosis GFP+ mice was higher than in the negative control group (p <0.05). In immunohistochemical tests, the rates of CD3, CD4, CD8 and IFN-γ positive cells was higher than in the positive control group, with their optical densities of 0.32 ± 0.63, 0.33 ± 0.00, 0.31 ± 0.91 and 0.28 ± 0.14 respectively (p <0.05). The expression of CD31 (0.19 ± 0.50) and VEGF (0.19 ± 0.21) were lower when compared with the positive control group, with no significant difference. CD31 and VEFG cell expression was low, at 0.19 ± 0.50 and 0.19 ± 0.21, respectively, compared with the positive control group (p >0.05). Values for CD31 and VEGF cells in the positive control group were higher, at 0.32 ± 0.35 and 0.29 ± 0.35, respectively, but when compared with the parabiosis tumour-bearing group, there was no significant difference. The expression of CD3, CD4, CD8 and IFN-γ cells at day 8 was low: 0.22, 0.17, 0.15 and 0.16, respectively. When compared with the parabiosis tumour-bearing group, there was no significant difference. CONCLUSIONS: The established allogeneic parabiosis mice model can be well adapted to the conjoined state of mice and be applied in wide medical experiments. The parabiosis model has played an important role in studying immune regulation, which provides a basis for the future tumour immunotherapy. Parabiosis models can stimulate tumour-bearing mice to generate CD3, CD4, CD8 and IFN-γ, and play a notable role in immune regulation and tumour destruction. The positive expression rates of CD31 and VEFG cells in the parabiosis tumour-bearing group were lower; however, when compared with the positive control group, there was no significant difference.

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells.

Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC-patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.

The natural history of naive T cells from birth to maturity.

Generating and maintaining a diverse repertoire of naive T cells is essential for protection against pathogens, and developing a mechanistic and quantitative description of the processes involved lies at the heart of our understanding of vertebrate immunity. Here, we review the biology of naive T cells from birth to maturity and outline how the integration of mathematical models and experiments has helped us to develop a full picture of their life histories.

Expression and Significance of Th17 and Treg Cells in Pulmonary Infections with Gram-Negative Bacteria.

The aim of this study was to investigate the expression and significance of T helper type 17 (Th17) and regulatory T (Treg) cells in severe pulmonary infection with gram-negative bacteria (GNB). The peripheral venous blood (PVB) and bronchoalveolar lavage fluid (BALF) were collected from patients receiving mechanical ventilation in the intensive care unit (ICU) owing to: (1) pulmonary GNB infection (group I) and (2) nonpulmonary infection (group NI). Patients from the two groups were matched based on their Acute Physiology and Chronic Health Evaluation II (APACHE II) scores and were recruited in the same period. The levels of Th17 and Treg cells in the PVB and BALF were measured by flow cytometry. (1) The levels of Th17 and Treg cells in the PVB and BALF of the infection group (I) were significantly higher than those of the noninfection group (NI) (p < 0.01), and the levels decreased significantly after treatment (p < 0.01). (2) The Treg/Th17 cell ratio in the PVB and BALF of group I was significantly lower than those of group NI and after treatment (p < 0.01). (3) The levels of Th17 and Treg cells in the PVB and BALF could not predict the 28-day mortality (p > 0.05). The expression of Th17 and Treg cells was abnormal in patients with severe pulmonary GNB infection. Our data suggest an overactive immune response in the early stages of inflammation, but the levels of Treg and Th17 cells failed to predict the 28-day mortality.

Circulating NK cells and their subsets in Behçet's disease.

Behçet's disease (BD) is an autoinflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood natural killer (NK) cells and their CD56Dim /CD56Bright subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-γ, granzyme B, perforin and the expression of degranulation marker CD107a. The effects of disease activity (BDActive versus BDQuiet ) and BD medication on NK cells were also investigated. Peripheral blood NK cells (P < 0·0001) and their constituent CD56Dim (P < 0·0001) and CD56Bright (P = 0·0015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive ) (P < 0·0001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P < 0·0001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P < 0·001). In general, CD56Dim cells produced more perforin (P < 0·0001) and granzyme B (P < 0·01) expressed higher CD16 levels (P < 0·0001) compared to CD56Bright cells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P < 0·01). Interestingly, IFN-γ production and CD27 expression were not significantly different between CD56Dim /CD56Bright subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.

Lower percentage of CD8+ T cells in peripheral blood of patients with sporotrichosis.

PURPOSE: To characterize the peripheral immunity and immunity response of patients with sporotrichosis, in this study we determined the lymphocyte subsets in the peripheral blood of Chinese patients with sporotrichosis. METHODS: In this retrospective study, peripheral blood was collected from 69 sporotrichosis patients (37, fixed cutaneous form; 32 lymphocutaneous) and 66 healthy controls. Lymphocyte subsets were analyzed using flow cytometry. RESULTS: Compared to controls, the percentage of CD8+ T cells was lower in sporotrichosis patients. The percentage of CD8+ T cells in peripheral blood tended to become lower with disease duration and disease severity, although the difference was not statistically significant for either acute, subacute and chronic patients or fixed cutaneous and lymphocutaneous patients. CONCLUSION: Our data indicate that the decrease of CD8+ T cells in peripheral blood of patients with sporotrichosis is associated with disease severity, although the difference was not statistically significant for either duration or clinical forms of the disease. Combining antifungal agents and immunomodulators in patients with long disease duration and lymphocutaneous may be more beneficial than antifungal monotherapy.

A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren's syndrome and systemic lupus erythematosus.

Follicular T helper (Tfh) cells have a crucial role in regulating immune responses within secondary lymphoid follicles by directing B cell differentiation towards memory B cells and plasma cells. Because abnormal humoral responses are key features in both primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection between peripheral Tfh cells and B cells in the two diseases. Twenty-five pSS patients, 25 SLE patients and 21 healthy controls were enrolled into the study. We determined the ratio of circulating Tfh-like cells, their interleukin (IL)-21 production and different B cell subsets by flow cytometry. We observed higher percentages of naive B cells in both diseases, while non-switched and switched memory B cells showed decreased frequencies. The proportions of double-negative B cells and plasmablasts were elevated in SLE and decreased in pSS. The percentages of transitional B cells and mature-naive B cells were higher in SLE. Patients with more severe disease course had an elevated ratio of TFH-like cells and increased IL-21 production. Moreover, expansion of Tfh-like cells correlated positively with parameters related to antibody secretion, including serum immunoglobulin (Ig)G, immune complexes (ICs) and autoantibodies. Correlation analysis between Tfh-like cells and certain B cell subsets revealed possible defects during B cell selection. In conclusion, our observations on the profound expansion of circulating Tfh-like cells and their IL-21 production, along with the characteristic aberrant peripheral B cell distribution in both pSS and SLE, indicate the prominent role of Tfh cell in the regulation of B cell selection.

Insight into normal thymic activity by assessment of peripheral blood samples.

The thymus is a highly specialized organ for T cell receptor (TCR) rearrangement and selection mechanisms that ensure the formation of functional and self-tolerant cells. Little is known about how peripheral blood assessment of thymic function reflects thymus activity during infancy. We compared thymic function-related markers in the thymus with those in peripheral blood in order to check their correlations. We concomitantly blood samples from immunocompetent infants who underwent cardiac surgery that involved thymectomy. The studied thymic markers included TCR excision circles (TRECs), four different TCRD (TCR delta chain) gene rearrangements, the TCR repertoire, regulatory T cells (Tregs, defined as the CD4+CD25+FOXP3+ cell population) and real-time quantitative polymerase chain reaction (RQ-PCR) mRNA expression of forkhead box P3 (FOXP3). Twenty patients were enrolled in this study. Their mean age at the time of the surgery was 3 months/5 days ± 3 months/18 days. There was a significant correlation between thymic and peripheral blood levels of TREC, all four TCRD gene rearrangements and the amount of Tregs. The levels of these parameters were significantly higher in the thymus than those detected in the peripheral blood. The TCR repertoire distribution in both samples was similar. FOXP3 mRNA levels in the thymus and peripheral blood correlated well. Our findings demonstrated a strong and significant correlation between peripheral blood and intra-thymic activity parameters during infancy. Assessment of these parameters in peripheral blood can be used to accurately estimate different intra-thymic capacities for assessing T cell function in health and disease.

Frequency and clonality of peripheral γδ T cells in psoriasis patients receiving anti-tumour necrosis factor-α therapy.

Hepatosplenic γδ T cell lymphoma (HSTCL) has been observed in patients with Crohn's disease (CD) who received anti-tumour necrosis factor (TNF)-α agents and thiopurines, but only one case was reported in a psoriasis patient worldwide. This difference could be due to differences in either the nature of the inflammatory diseases or in the use of immunomodulators. We investigated the impact of anti-TNF-α agents on the level and repertoire of γδ T cells in peripheral blood from psoriasis patients. Forty-five men and 10 women who were treated with anti-TNF-α agents for psoriasis were monitored for a median 11 months for the level and clonality of γδ T cells via flow cytometry and polymerase chain reaction (PCR) analysis of T cell receptor gamma (TCR-γ) gene rearrangements. Seventeen men had a repeated analysis within 48 h of the infliximab infusion to reveal a possible expansion of γδ T cells, as observed previously in CD patients. Ten psoriasis patients who were never exposed to biologicals and 20 healthy individuals served as controls. In the majority of psoriasis patients, the level and clonal pattern of γδ T cells was remarkably stable during infliximab treatment. A single male patient repeatedly experienced a significant increase in the level of γδ T cells after infliximab infusions. A monoclonal γδ T cell repertoire in a polyclonal background tended to be more frequent in anti-TNF-α-treated patients than naive patients, suggesting that anti-TNF-α therapy may promote the clonal selection of γδ T cells in psoriasis patients.

Variable immune cell frequencies in peripheral blood of LEW.1AR1-iddm rats over time compared to other congenic LEW strains.

The LEW.1AR1-iddm rat is an animal model of human type 1 diabetes (T1D), which arose through a spontaneous mutation within the major histocompatibility complex (MHC)-congenic background strain LEW.1AR1. The LEW.1AR1-iddm rat is characterized by two phenotypes: diabetes development with a diabetes incidence of 60% and a variable T cell frequency in peripheral blood. In this study the immune cell repertoire of LEW.1AR1-iddm rats was analysed over time from days 30 to 90 of life and compared to the background strain LEW.1AR1 and the LEW rat strain as well as the LEW.1WR1 rat strain. The LEW.1AR1-iddm rats are characterized by a high variability of CD3(+), CD4(+) and CD8(+) T cell frequencies in peripheral blood over time, and the frequency is unique for each animal. The variability within the frequencies resulted in changes of the CD4(+) : CD8(+) T cell ratio. The other three rat strains studied were characterized by a stable but nevertheless strain-specific T cell frequency resulting in a specific CD4(+) : CD8(+) T cell ratio. The frequency of natural killer (NK) cells and B cells in LEW.1AR1-iddm rats was increased, with a higher variability compared to the other strains. Only monocytes showed no differences in frequency and variability between all strains studied. These variabilities of immune cell frequencies in the LEW.1AR1-iddm rats might lead to imbalances between autoreactive and regulatory T cells in peripheral blood as a prerequisite for diabetes development.

Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment.

Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.

A divergent response of innate regulatory T-cells to sepsis in humans: circulating invariant natural killer T-cells are preserved.

BACKGROUND: Sepsis is associated with severe immunosuppression, evidenced by loss and dysfunction of CD3(+) lymphocytes and γδ-TCR(+) T-cells. There is limited data addressing changes in the invariant natural killer T-(iNKT) cell population with sepsis, and whether such changes correlate with clinical outcomes. Specifically, septic geriatric patients have marked mortality. How γδ-TCR(+) T-cells and iNKT-cells are altered in the settings of sepsis and advanced age, and how these changes correlate with mortality are unknown. METHODS: 49 young (18-50years) and 55 geriatric (>65years) ICU patients with confirmed sepsis were enrolled. Blood was stained with antibodies to detect the percentage and absolute number of CD3(+) (T-cells), γδ-TCR(+) T-cell, TCR-Vα-24(+) (iNKT-cells), and CD69(+) (marker of cell activation). Blood from 10 healthy controls was also collected. RESULTS: Septic patients displayed marked leukocytosis, decreased CD3(+) lymphocytes, and γδ-TCR(+) T-cells, and increased percentage and number of iNKT-cells. Young and geriatric patients had similar degree of leukocytosis, along with percentage, number, and %CD69(+) CD3(+) T-cell and γδ-TCR(+) T-cells; however, percentage, number, and %CD69(+)iNKT-cells were most markedly elevated in geriatric patients. Geriatric non-survivors had higher percentage and number of, but decreased %CD69(+), iNKT-cells vs survivors. CONCLUSIONS: iNKT-cells are increased in sepsis, suggesting that they typify an evolving morbid state. This is most pronounced in geriatric non-survivors, a group demonstrating dysfunctional regulatory iNKT-cell phenotype.

Cyclic changes and relationship between peripheral and endometrial NK cells from women with repeated failure after artificial insemination by donor sperm.

PROBLEM: Cyclic changes of peripheral natural killer (pNK) cells and/or endometrial NK (eNK) cells during menstrual cycle remain controversial, and their relationship remains uncertain. METHOD OF STUDY: Peripheral blood and endometrial biopsies were simultaneously obtained from women (n = 23) undergoing artificial insemination with donor sperm (AID) for at least three cycles at both proliferative (days 9-11) and secretory phases (days 20-23) of menstrual cycle. The percentages of CD3(-) CD56(+), CD3(-) CD56(dim) CD16(+), CD3(-) CD56(bright) CD16(-) pNK, and eNK cell subsets within lymphocytes were determined by three-color flow cytometry. The correlation between the percentages of pNK and eNK cells was further analyzed by Spearman's test. RESULTS: The percentages of CD3(-) CD56(+), CD3(-) CD56(dim) CD16(+), and CD3(-) CD56(bright ) CD16(-) pNK cells were not statistically different between the proliferative and secretory phases (P > 0.05, respectively). However, the percentages of CD3(-) CD56(+) and CD3(-) CD56(bright ) CD16(-) eNK cells were significantly decreased at the secretory phase, compared with those in the proliferative phase (P < 0.05, respectively). No correlation between the percentages of all pNK cell parameters and those of CD3(-) CD56(bright ) CD16(-) eNK cells (the major subset of NK cells in uterus) was found in the same women throughout the menstrual cycle (P > 0.05). CONCLUSION: We found a menstrual-cycle-dependent change in the percentage of eNK cells in women undergoing AID treatment, but not pNK cells. Moreover, the percentage of pNK cells may not reflect that of eNK cells during menstrual cycle.

Maternal circulating dendritic cell subtypes at delivery and during the 1-year postpartum period.

PROBLEM: Dendritic cells (DCs) play an important role in maintaining pregnancy by inducing tolerance toward the fetus. Such an immunologic change in the mother should be restored to normal after delivery, but few studies have reported postpartum maternal immune recovery, in terms of the types circulating DCs. METHOD OF STUDY: The level of each DC subtype and HLA-DR-positive immunoreactivity of the blood from 29 pregnant women with uncomplicated labor was serially analyzed by flowcytometry at delivery and at 1.5, 6, and 12 months after delivery. DC subtypes were characterized as myeloid, lymphoid, and less differentiated (ldDC). Mean fluorescence intensity (MFI) was evaluated for HLA-DR expression for each DC subtype. RESULTS: The total number and the percentage of DCs at delivery were lower than those at 12 months postpartum. The ldDC fractions were significantly higher at delivery and at 1.5 months than at 12 months postpartum. The MFI of HLA-DR expression on ldDCs at delivery was lower than that at 12 months postpartum. The myeloid-to-lymphoid DC ratio did not differ over the 1-year postpartum period. CONCLUSION: The maternal alteration in DCs rapidly normalized within 1.5 months, except for the ldDC fraction, which persisted between 1.5 and 6 months after delivery.

Acute coronary syndromes are associated with a reduction of VLA-1+ peripheral blood T cells and their enrichment in coronary artery plaque aspirates.

Memory T cells producing interferon (IFN)γ and expressing very late antigen-1 (VLA-1) integrin collagen receptors are found in carotid atherosclerotic plaques, suggesting their involvement in coronary artery disease (CAD) as well. To determine the role of VLA-1+ T cells in CAD percent of CD3+ T cells binding monoclonal antibodies (mAb) to VLA-1 in peripheral blood (PB), and in coronary plaque material aspirated during coronary arterography and arterial blood, were analyzed in a cohort of 117 patients with CAD and 34 controls without CAD. % VLA-1+ T cells in PB was 0.63 ± 0.09% in controls compared to 0.96 ± 0.95% in patients with CAD (p<0.009). The increase was due to a marked elevation of % VLA-1+ T cells in stable CAD (1.6 ± 0.27%) whereas % VLA-1+ T cells during acute coronary syndromes (ACS) and in patients with ischemia by thalium SPECT scan had significantly lower levels. % VLA-1+ T cells in coronary artery plaque material aspirated during therapeutic angiography in patients with ACS was significantly higher than in arterial blood (1.39 ± 0.96% vs 0.75 ± 0.84%, p<0.035, n=3). Thus, % VLA-1+ T cells increases in the PB during stable CAD but decreases in ACS. The finding of their enrichment in coronary blood containing atherosclerotic plaque aspirates suggests that a shift of VLA-1+ T cells from blood to atherosclerotic plaques may play a role in plaque instability in patients with ACS.

The secretion of IL-22 from mucosal NKp44⁺ NK cells is associated with microbial translocation and virus infection in SIV/SHIV-infected Chinese macaques.

Microbial translocation (MT) causes systemic immune activation in chronic human immunodeficiency virus (HIV) infection. The role of a novel subtype of innate lymphoid cells, the NKp44(+) NK cells, in HIV/simian immunodeficiency virus- (SIV-) induced MT remains unknown. In this study, 12 simian-human immunodeficiency virus- (SHIV-) infected macaques were chosen and split into two groups based on the MT level. Blood and Peripheral lymphoid tissue were sampled for flow cytometric analysis, viral load detection, and interleukin testing. Then, six naive Chinese macaques were used to determine the dynamics of cytokine secretion from mucosal NKp44(+) NK cells in different phases of SIV infection. As a result, the degranulation capacity and IL-22 production of mucosal NKp44(+) NK cells were associated with the MT level in the SHIV-infected macaques. And the number of mucosal NKp44(+) NK cells and IL-22 secretion by these cells were lower in the chronic phase than in the early acute phase of SIV infection. The number of mucosal NKp44(+) NK cells and interleukin-22 (IL-22) secretion by these cells increased before MT occurred. Therefore, we conclude that a decline in IL-22 production from mucosal NKp44(+) NK cells induced by virus infection may be one of the causes of microbial translocation in HIV/SIV infection.

The peripheral blood compartment in patients with Graves' disease: activated T lymphocytes and increased transitional and pre-naive mature B lymphocytes.

Graves' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)⁺ and CD25⁺] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38(high) CD27⁻, P < 0.03) and pre-naive mature (CD38(low) CD27⁻ IgD⁺ CD5⁺, P < 0.04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5⁺, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5⁺ B lymphocytes within the peripheral blood. The increase in CD5⁺ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5⁺ B lymphocytes.

Low levels of insulin-like growth factor-1 contribute to alveolar macrophage dysfunction in cystic fibrosis.

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from cystic fibrosis (CF) transmembrane conductance regulator(-/-) mice have impaired function, no study has investigated primary alveolar macrophages in adults with CF. CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from eight CF subjects and eight healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared with control subjects. CF subjects had lower serum and BAL IGF-1 levels compared with healthy control subjects. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, whereas IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment.