TY - JOUR
KW - Adaptor Proteins, Signal Transducing
KW - Amino Acid Sequence
KW - Antibodies, Monoclonal
KW - Antigens, Bacterial
KW - CTLA-4 Antigen
KW - Cell Lineage
KW - Cell Wall
KW - Cells, Cultured
KW - Cytokines
KW - Disease Progression
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Humans
KW - Immune Tolerance
KW - Immunity, Cellular
KW - Leprosy, Multibacillary
KW - Leprosy, Paucibacillary
KW - Molecular Sequence Data
KW - Mycobacterium leprae
KW - Proto-Oncogene Proteins c-cbl
KW - RNA, Small Interfering
KW - T-Lymphocytes, Regulatory
KW - Th1 Cells
KW - Th2 Cells
KW - Transforming Growth Factor beta
AU - Kumar S
AU - Naqvi R
AU - Khanna N
AU - Pathak P
AU - Rao D N
AB - <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>
BT - Clinical immunology (Orlando, Fla.)
C1 - http://www.ncbi.nlm.nih.gov/pubmed/21807564?dopt=Abstract
DA - 2011 Nov
DO - 10.1016/j.clim.2011.06.007
IS - 2
J2 - Clin. Immunol.
LA - eng
N2 - <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>
PY - 2011
SP - 133
EP - 42
T2 - Clinical immunology (Orlando, Fla.)
TI - Th3 immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b.
VL - 141
SN - 1521-7035
ER -