Functional inhibitory receptors expressed by a cutaneous T cell lymphoma-specific cytolytic clonal T cell population

Inhibitory receptors on natural killer cells and on a minority of T lymphoc ytes are major histocompatibility complex class Ia or Ib specific. We have previously reported several tumor-specific cytotoxic T cell clones infiltra ting a CD4+ V beta 13(+) cutaneous T cell lymphoma. These clones mediated a specific major histocompatibility complex class I-restricted cytotoxic act ivity toward the uncultured tumor cells and autologous long-term tumor T ce ll lines. In this study, we cultured with interleukin-2 the peripheral bloo d lymphocytes of the same patient a few weeks before invasion of the blood by tumor cells. We report the rapid and selective expansion of a CD8(+) V b eta 13(+) lymphoid population. This population was clonal, as it expressed a unique T cell receptor-V beta junctional region. V beta 13(+) tumor cells and V beta 13(+) reactive T cells were shown to have different junctional sequences. The CD8(+) reactive clone was functional, as it had a specific a utologous tumor-specific, human leukocyte antigen-A2 restricted, cytotoxic activity. This clone coexpressed high levels of CD158a, CD158b, p70, and CD 94/NKG2A inhibitory receptors, Interestingly, we found that anti-CD158a and anti-CD158b monoclonal antibodies could inhibit anti-CD3 redirected cytoto xicity mediated by the reactive clonal population. Further, an anti-human l eukocyte antigen-B/C monoclonal antibody enhanced the specific cytotoxic ac tivity of the clone against autologous tumor cells. These results are the f irst evidence that inhibitory receptor expression can lead to the inhibitio n of cutaneous T cell lymphoma-specific T cell responses.