Abstract
The immune attack against malignant tumors require the concerted action of CD8(+) cytotoxic T lymphocytes (CTL) as well as CD4(+) T helper cells. The contribution of T cell receptor (TCR) alpha beta(+) CD4(-) CD8(-) double-negative (DN) T cells to anti-tumor immune responses is widely unknown. In previous studies, we have demonstrated that DN T cells with a broad TCR repertoire are present in ...
Abstract
The immune attack against malignant tumors require the concerted action of CD8(+) cytotoxic T lymphocytes (CTL) as well as CD4(+) T helper cells. The contribution of T cell receptor (TCR) alpha beta(+) CD4(-) CD8(-) double-negative (DN) T cells to anti-tumor immune responses is widely unknown. In previous studies, we have demonstrated that DN T cells with a broad TCR repertoire are present in humans in the peripheral blood and the lymph nodes of healthy individuals. Here, we characterize a human DN T cell clone (T4H2) recognizing an HLA-A2-restricted melanoma-associated antigenic gp100-peptide isolated from the peripheral blood of a melanoma patient. Antigen recognition by the T4H2 DN clone resulted in specific secretion of IFN-gamma and TNF. Although lacking the CD8 molecule the gp100-specifc DN T cell clone was able to confer antigen-specific cytotoxicity against gp100-loaded target cells as well as HLA-A2(+) gp100 expressing melanoma cells. The cytotoxic capacity was found to be perforin/granzymeB-dependent. Together, these data indicate that functionally active antigen-specific DN T cells recognizing MHC class I-restricted tumor-associated antigen (TAA) may contribute to anti-tumor immunity in vivo.
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