02399nas a2200361   4500000000100000008004100001260001300042653002500055653002400080653001700104653003100121653003000152653001100182653002300193653002100216653002500237653002600262653002500288653003900313653001700352653001800369653001800387653001400405100001600419700001400435700001700449700001800466245013300484300001100617490000700628520138800635022001402023       2000                            d  c2000 Aug10aAntigen Presentation10aAntigens, Bacterial10aCD4 Antigens10aCD4-Positive T-Lymphocytes10aCytotoxicity, Immunologic10aHumans10aImmunity, Cellular10aInterferon-gamma10aLeprosy, Tuberculoid10aLymphocyte Activation10aMycobacterium leprae10aPeripheral Nervous System Diseases10aPhagocytosis10aSchwann Cells10aT-Lymphocytes10aTh1 Cells1 aSpierings E1 aDe Boer T1 aZulianello L1 aOttenhoff T H00aNovel mechanisms in the immunopathogenesis of leprosy nerve damage: the role of Schwann cells, T cells and Mycobacterium leprae.  a349-550 v783 a<p>The major complication of reversal (or type 1) reactions in leprosy is peripheral nerve damage. The pathogenesis of nerve damage remains largely unresolved. In situ analyses suggest an important role for type 1 T cells. Mycobacterium leprae is known to have a remarkable tropism for Schwann cells that surround peripheral axons. Reversal reactions in leprosy are often accompanied by severe and irreversible nerve destruction and are associated with increased cellular immune reactivity against M. leprae. Thus, a likely immunopathogenic mechanism of Schwann cell and nerve damage in leprosy is that infected Schwann cells process and present antigens of M. Leprae to antigen-specific, inflammatory type 1 T cells and that these T cells subsequently damage and lyse infected Schwann cells. Previous studies using rodent CD8+ T cells and Schwann cells have revealed evidence for the existence of such a mechanism. Recently, a similar role has been suggested for human CD4+ T cells. These cells may be more important in causing leprosy nerve damage in vivo, given the predilection of M. leprae for Schwann cells and the dominant role of CD4+ serine esterase+ Th1 cells in leprosy lesions. Antagonism of molecular interactions between M. leprae, Schwann cells and inflammatory T cells may therefore provide a rational strategy to prevent Schwann cell and nerve damage in leprosy.</p>  a0818-9641