02505nas a2200481   4500000000100000008004100001260001300042653004100055653002400096653002700120653002400147653001900171653001700190653001400207653002000221653001400241653002400255653003000279653003100309653001100340653002100351653002300372653002800395653002800423653002800451653002500479653003400504653002700538653003000565653001400595653001400609653003600623100001200659700001200671700001300683700001300696700001200709245011000721300001100831490000800842520115900850022001402009       2011                            d  c2011 Nov10aAdaptor Proteins, Signal Transducing10aAmino Acid Sequence10aAntibodies, Monoclonal10aAntigens, Bacterial10aCTLA-4 Antigen10aCell Lineage10aCell Wall10aCells, Cultured10aCytokines10aDisease Progression10aGene Expression Profiling10aGene Expression Regulation10aHumans10aImmune Tolerance10aImmunity, Cellular10aLeprosy, Multibacillary10aLeprosy, Paucibacillary10aMolecular Sequence Data10aMycobacterium leprae10aProto-Oncogene Proteins c-cbl10aRNA, Small Interfering10aT-Lymphocytes, Regulatory10aTh1 Cells10aTh2 Cells10aTransforming Growth Factor beta1 aKumar S1 aNaqvi R1 aKhanna N1 aPathak P1 aRao D N00aTh3 immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b.  a133-420 v1413 a<p>Leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. Comprehensive-expressional-profiling of Th1-Th2-Th3 associated markers (84 genes) using qRT-PCR array, negated the previously prevailing notion, Th2 bias towards multibacillary stage of leprosy. High production TGF-β further supported the dearth of any immune response(s) in leprosy progression. Over expression of Cbl-b, could emerge as plausible reason for contributing T cell hyporesponsiveness, possibly by degradation of T cells signaling molecules. Anti-TGF-β treatments further confirm the TGF-β-dependent-Cbl-b overexpression in multibacillary patients. Diminished Cbl-b expression in CTLA-4 knockout studies using siRNA, provided other evidence towards T cell hyporesponsiveness. Further, high T cell proliferation and IL-2 production in PBMC cultures treated with anti-TGF-β and siRNA offers here a strategy to revert T cell hyporesponsiveness by downregulating Cbl-b expression in leprosy. Thus, this study negates Th2 bias and substantiates molecular cross-talk amongst TGF-β-CTLA-4-Cbl-b eventually leads to M. leprae persistence.</p>  a1521-7035