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. 1990 Jun 1;171(6):2011–2024. doi: 10.1084/jem.171.6.2011

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

PMCID: PMC2187955  PMID: 1972178

Abstract

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

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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