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Th3 Immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b

Clinical Immunology, ISSN: 1521-6616, Vol: 141, Issue: 2, Page: 133-142
2011
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Article Description

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.

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