The role of human type 1 effector T cells in the immune response to infection can be readily studied in leprosy, an infectious disease where type 1 responses correlate with the clinical manifestations of the disease. Tuberculoid (T-lep) and reversal reaction leprosy patients exhibit an inflammatory cell-mediated immune response (Th1) against Mycobacterium leprae infection, whereas lepromatous (L-lep) leprosy patients exhibit a humoral, anti-inflammatory (Th2) response. We have previously shown that T cell receptor (TCR) Vbeta6+ T cells are clonally expanded in T-lep and reversal reaction patients, but not in L-lep patients. In our current studies, we derived from a leprosy lesion a T cell clone bearing Vbeta6 that recognizes a large MW, basic, conserved mycobacterial antigen which we have partially characterized as having a MW of 150kD and an isoelectric focusing point of pI 8. The TCR Vbeta6+ T cell subpopulation produces a Th1 cytokine pattern, directly lyses M. leprae-pulsed antigen presenting cells by the granule exocytosis pathway, and expresses the antimicrobial protein granulysin. Vbeta6+ T cells may therefore contribute to the cell mediated immune response against M. leprae. |