The Distribution of Activation Markers and Selectins on Peripheral T Lymphocytes in Preeclampsia

INTRODUCTION: Impaired maternal immune tolerance resulting in systemic inflammation plays a pivotal role in the pathogenesis of preeclampsia. Phenotypical changes of monocytes and neutrophil granulocytes have already been studied in preeclampsia, and some studies also included T lymphocyte activation markers; however, the results are controversial and a comprehensive analysis of activation markers is lacking. The characteristics of cellular adhesion molecules in preeclampsia are yet to be described. MATERIAL AND METHODS: Peripheral blood samples of 18 preeclamptic patients and 20 healthy pregnant women in the third trimester were evaluated using flow cytometry to characterize the cell surface expression of T lymphocyte activation markers and selectins. RESULTS: We found an elevated ratio of HLA-DR and CD122-, CD62E-, and CD62L-expressing cells among the CD4+ T lymphocytes in PE in comparison to healthy pregnancy. No alterations were found in the prevalence of CD69-, CD25-, and CD62P-expressing lymphocytes and CD11c-expressing monocytes. CONCLUSIONS: Our findings support the role of activated T lymphocytes and specific cell adhesion molecules in the pathogenesis of preeclampsia

The effects of Kv1.3 and IKCa1 channel inhibition on cytokine production and calcium influx of T lymphocytes in rheumatoid arthritis and ankylosing spondylitis

Kv1.3 and IKCa1 lymphocyte potassium channels have been implicated as important targets of selective immunomodulation. We compared the alterations in cytokine production upon selective inhibition of Kv1.3 or IKCa1 channels (by MGTX and TRAM, respectively) in healthy donors (HD), RA and AS patients. We also determined calcium influx kinetics and its sensitivity to Kv1.3 and IKCa1 channel inhibition following PHA activation in CD4, Th1, Th2 and CD8 cells as well as monocytes. The application of TRAM resulted in a lower production of TNF-a and IL1-RA in all three study groups. Inhibition by TRAM had contrary effects on the production of IL-1b and IL-5: While their production was increased by PBMCs of RA patients, this effect was not observed in HD and AS PBMCs. While treatment with MGTX resulted in a similar decrease in calcium influx in the CD4 and Th2 subsets across all study groups, TRAM treatment had opposite effects on RA and HD samples: It decreased calcium influx in the Th2 and CD8 subsets in RA, while only Th1 cells were affected in HDs. The effects of IKCa1 channel inhibition are controversial in samples of RA and AS patients, since it shifts the inflammatory balance into the pro-inflammatory direction

T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: ( 1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; ( 2) in anti-TNF responders as well as in nonresponders, the frequencies of naive CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; ( 3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; ( 4) pending confirmation, a CD4CD69 ratio <2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA

Altered mitochondrial response to activation of T-cells in neonate

Mitochondrial functions have a major impact on T-cell functionality. In this study we characterized whether mitochondrial function in the neonatal T-cells differs from that in the adult T-cells during short T-cell activation. METHODS: We used fow cytometry methods to test mitochondrial mass and to monitor mitochondrial Ca(2+) levels, mitochondrial potential and superoxide generation in parallel with cytoplasmic Ca(2+) levels during phythohaemagglutinine-induced activation of CD4+ and CD8+ T-cells of 12 term neonates and 11 healthy adults. RESULTS: Baseline mitochondrial mass of CD4+ and CD8+ cells was lower in the neonate than in the adult. In comparison with the adult, neonatal resting CD4+ T-cells had lower cytoplasmic Ca(2+) levels and this was associated with normal activation induced Ca(2+)-response. During short-term activation cytoplasmic Ca(2+)-response was lower in neonatal than in adult CD8+ T-cells. Mitochondrial Ca(2+) uptake was increased in CD4+ neonatal T cells while it decreased in CD8+ T-cells. Mitochondrial depolarization was increased in CD4+ and decreased in CD8+ neonatal T-cells compared to adults. Superoxide generation was higher and equal in neonatal CD4+ and CD8+ cells, respectively, compared to the adult ones. CONCLUSION: Our data suggest that neonatal T-cells exhibit marked differences in mitochondrial function and superoxide generation compared to adult T-cells

A terápiás célú teljestest-hypothermia szisztémás és immunmoduláns hatásai = Systemic and immunomodulatory effects of whole body therapeutic hypothermia

A központi idegrendszert érintő ischaemia-reperfúziós károsodás kialakulásában számos neurobiológiai folyamat vesz részt, amit terápiás hypothermia révén kedvezően lehet befolyásolni. A terápiás hypothermiát napjainkban a stroke, a perinatalis asphyxia, illetve a szívinfarktus-eredetű klinikai halál állapotával kapcsolatos neurológiai szövődmények kivédése érdekében egyre szélesebb körben alkalmazzák. A hypothermia idegrendszeri hatásai mellett szisztémás hatásokkal is rendelkezik. Befolyásolja az izmok, a cardiovascularis rendszer működését, elektroliteltéréseket okoz, befolyásolja a szisztémás anyagcserét, illetve több megfigyelés szerint a gyulladást is csökkenti. Összefoglaló közleményünkben a terápiás hypothermia szisztémás immunrendszerre gyakorolt hatásait tekintjük át. Sejtszintű vizsgálatok, állatkísérletes adatok és humán megfigyelések alapján a rövid távú (2–4 órás) hypothermia az antiinflammatorikus citokinek szintjét emeli, illetve csökkenti a proinflammatorikus citokinek szintjét. Tartós hypothermia (>24 óra) esetén azonban a proinflammatorikus citokinszintek emelkednek. A hypothermia csökkenti továbbá a lymphocytaproliferációt és gátolja az endotoxinnal aktivált lymphocytákban a HLA-DR expresszióját. Ezek az adatok jelzik a szisztémásan alkalmazott terápiás célú hypothermia immunmoduláns hatását. Azt, hogy az immunmoduláció milyen mértékben járul hozzá a központi idegrendszer védelméhez, további vizsgálatoknak kell kimutatnia. Orv. Hetil., 2011, 152, 575–580. | Several neurobiological mechanisms contribute to the development of ischemic-reperfusion damage of the central nervous system that may be modulated by hypothermia. Nowadays hypothermia is a therapeutic tool for the treatment of stroke and perinatal asphyxia. Hypothermia does not only affect the central nervous system, but also has systemic effects. It influences the muscular and cardiovascular system, the systematic metabolism, induces electrolyte changes, and decreases inflammation. This review summarizes the effects of therapeutic hypothermia on the immune system. Experiments on cell lines and in animals along with human experience indicate that short term (2-4 hours) hypothermia increases the levels of anti-inflammatory cytokines and decreases that of proinflammatory cytokines. Long term (>24 hours) hypothermia, however, increases proinflammatory cytokine levels. Furthermore, hypothermia inhibits lymphocyte proliferation and decreases HLA-DR expression associated with cell activation. These results suggest that therapeutic hypothermia has a systemic immunomodulatory effect. Further research is required to determine the contribution of immunomodulation to the defense of the central nervous system. Orv. Hetil., 2011, 152, 575–580