02766nas a2200361   4500000000100000008004100001260001300042653002200055653001200077653002400089100001400113700001300127700001800140700001300158700001300171700002300184700001200207700001400219700001300233700001500246700001200261700001700273700001300290700001600303700001200319245004600331856007700377300001000454490000600464050001700470520190300487022001402390       2014                            d  c2014 Apr10aT-cell regulation10aleprosy10alepromatous leprosy1 aBobosha K1 aWilson L1 aMeijgaarden K1 aBekele Y1 aZewdie M1 aPloeg-van Schip JJ1 aAbebe M1 aHussein J1 aKhadge S1 aNeupane KD1 aHagge D1 aJordanova ES1 aAseffa A1 aOttenhoff T1 aGeluk A00aT-cell regulation in lepromatous leprosy.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983090/pdf/pntd.0002773.pdf  ae27730 v8  aBOBOSHA 20143 a<p>Regulatory T (Treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. However, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (TB). Despite high humoral responses against Mycobacterium leprae (M. leprae), lepromatous leprosy (LL) patients have the characteristic inability to generate T helper 1 (Th1) responses against the bacterium. In this study, we investigated the unresponsiveness to M. leprae in peripheral blood mononuclear cells (PBMC) of LL patients by analysis of IFN-γ responses to M. leprae before and after depletion of CD25+ cells, by cell subsets analysis of PBMC and by immunohistochemistry of patients' skin lesions. Depletion of CD25+ cells from total PBMC identified two groups of LL patients: 7/18 (38.8%) gained in vitro responsiveness towards M. leprae after depletion of CD25+ cells, which was reversed to M. leprae-specific T-cell unresponsiveness by addition of autologous CD25+ cells. In contrast, 11/18 (61.1%) remained anergic in the absence of CD25+ T-cells. For both groups mitogen-induced IFN-γ was, however, not affected by depletion of CD25+ cells. In M. leprae responding healthy controls, treated lepromatous leprosy (LL) and borderline tuberculoid leprosy (BT) patients, depletion of CD25+ cells only slightly increased the IFN-γ response. Furthermore, cell subset analysis showed significantly higher (p = 0.02) numbers of FoxP3+ CD8+CD25+ T-cells in LL compared to BT patients, whereas confocal microscopy of skin biopsies revealed increased numbers of CD68+CD163+ as well as FoxP3+ cells in lesions of LL compared to tuberculoid and borderline tuberculoid leprosy (TT/BT) lesions. Thus, these data show that CD25+ Treg cells play a role in M. leprae-Th1 unresponsiveness in LL.</p>
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