Sister cytotoxic CD8+ T cell clones differing in natural killer inhibitory receptor expression in human astrocytoma

Natural killer (NK) inhibitory receptors are thought to play a critical role in the regulation of cytotoxicity of NK cells and certain self-reactive T cells. In the present study, we investigated whether astrocytoma infiltrating T lymphocytes may be functionally compromised by NK receptors (NKRs). The NK inhibitory receptor CD94/NKG2A was found on a significant proportion of CD8+ astrocytoma infiltrating lymphocytes. The functional consequences of CD94/NKG2A expression were explored at the clonal level, using a T cell clone that exhibited substantial variation in the expression of this heterodimer. Triggering of CD94/NKG2A inhibited the killing properties of T cells with a high level of this receptor, but not those from T cells with a low level. Our data indicate that some astrocytoma infiltrating lymphocytes express functional inhibitory CD94/NKG2A, raising the possibility that they may represent silent T cells specific for self-antigens (Ags) expressed on tumor cells. Understanding the mechanisms of regulation of these receptors may bring new insights for optimizing an anti-tumor immune response.