Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas

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Abstract
In this study, we showed that renal tumors contain substantial subsets of CD8+ p58+ T cells. From 1 of these tumors, T cells were amplified in mixed lymphocytes–tumor cell cultures and p58+ T cells were selected immunologically. After expansion, phenotypic and functional features of p58+ and p58− T cells were examined. The p58+ T cells expressed p58.2 receptor and corresponded to CD3+, CD8+, T-cell receptor (TCR) /β+ T cells that were CD56+ and CD28−. Functionally, p58+ T cells showed a low level of lytic activity against autologous tumor cells that was dramatically and specifically increased by anti-p58.2 monoclonal antibody. On the other hand, p58− CD8+ T cells did not lyse autologous tumor cells and had non-major histocompatibility complex–restricted cytotoxicity against K562 and Daudi cells. A p58+ cytotoxic T lymphocyte (CTL) clone (4C7) with the same characteristics as the p58+ T-cell line was derived. This CTL clone did not lyse autologous normal B cells but lysed several HLA-A1+ renal tumor cell lines. Analysis of TCR repertoire diversity showed that the p58+T-cell line contained 3 TCR rearrangements, whereas the TCR repertoire of p58− T cells was polyclonal. Interestingly, TCR transcripts of p58+ T cells and of CTL clone 4C7 were detected as prominent ex vivo in tumor cells but not in peripheral blood mononuclear cells, suggesting that these cells are antigen specific and amplified at the tumor site.

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