@article{22179,
  keywords = {Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antibodies, Monoclonal, Antigens, Bacterial, CTLA-4 Antigen, Cell Lineage, Cell Wall, Cells, Cultured, Cytokines, Disease Progression, Gene Expression Profiling, Gene Expression Regulation, Humans, Immune Tolerance, Immunity, Cellular, Leprosy, Multibacillary, Leprosy, Paucibacillary, Molecular Sequence Data, Mycobacterium leprae, Proto-Oncogene Proteins c-cbl, RNA, Small Interfering, T-Lymphocytes, Regulatory, Th1 Cells, Th2 Cells, Transforming Growth Factor beta},
  author = {Kumar S and Naqvi R and Khanna N and Pathak P and Rao D N},
  title = {Th3 immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b.},
  abstract = {<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>},
  year = {2011},
  journal = {Clinical immunology (Orlando, Fla.)},
  volume = {141},
  pages = {133-42},
  month = {2011 Nov},
  issn = {1521-7035},
  doi = {10.1016/j.clim.2011.06.007},
  language = {eng},
}