Specific killing of cytotoxic T cells and antigen-presenting cells by CD4+ cytotoxic T cell clones. A novel potentially immunoregulatory T-T cell interaction in man.

摘要: Mycobacterial antigens not only stimulate Th cells that produce macrophage-activating factors, but also CD4+ and CD8+ CTL lyse human macrophages. The mycobacterial recombinant 65-kD hsp was previously found to be an important target antigen for polyclonal CTL. Because of the major role in immune response as well autoantigens, we have studied activity this protein at clonal level. HLA-DR or HLA-DQ restricted, CD4+CD8- T cell clones recognize different peptides M. leprae strongly lysed EBV-BLCL pulsed with specific irrelevant peptide. No bystander lysis B cells, tumor seen. Target could triggered by PMA + Ca2+ ionophore alone depended on active metabolism. Interestingly, these themselves other HLA-class II compatible (TCR-alpha/beta -gamma/delta) presence peptide, suggesting are actively protected from CTL-mediated lysis. Cold competition experiments suggested targets were more efficiently recognized than targets. These results demonstrate hsp65 peptide-specific HLA class II-restricted display strong peptide-dependent cytolytic towards both APCs, and, unexpectedly, clones, including themselves. Since, contrast murine express II, killing may represent a novel immunoregulatory pathway man.