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.
Perrin
Gaëlle
G
Laboratory of Tumor Immunology, Division of Oncology, University Hospital, 1211 Geneva 14, Switzerland.
Speiser
Daniel
D
Porret
Andrée
A
Quiquerez
Anne-Lise
AL
Walker
Paul R
PR
Dietrich
Pierre-Yves
PY
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D001254:Astrocytoma / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell