HLA class I-specific inhibitory receptors in human T lymphocytes: Interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ …

MC Mingari, M Ponte, S Bertone… - Proceedings of the …, 1998 - National Acad Sciences
MC Mingari, M Ponte, S Bertone, F Schiavetti, C Vitale, R Bellomo, A Moretta, L Moretta
Proceedings of the National Academy of Sciences, 1998National Acad Sciences
A fraction of human T lymphocytes, predominantly CD8+, express receptors for HLA class I
molecules typical of natural killer cells (natural killer receptors or NKRs) that inhibit T cell
receptor-mediated functions. Herein, we analyzed possible mechanism (s) leading to the
expression of NKRs by T cells responding to superantigens or allogeneic cells in vitro. We
show that, in the presence of interleukin 15 (IL-15), T cells (depleted of NKR+ cells)
responding to toxic shock syndrome toxin 1 de novo express CD94, a molecule that is part of …
A fraction of human T lymphocytes, predominantly CD8+, express receptors for HLA class I molecules typical of natural killer cells (natural killer receptors or NKRs) that inhibit T cell receptor-mediated functions. Herein, we analyzed possible mechanism(s) leading to the expression of NKRs by T cells responding to superantigens or allogeneic cells in vitro. We show that, in the presence of interleukin 15 (IL-15), T cells (depleted of NKR+ cells) responding to toxic shock syndrome toxin 1 de novo express CD94, a molecule that is part of a heterodimeric NKR with a broad specificity for different HLA class I alleles. Maximal CD94 expression occurred when IL-15 was added shortly after the cells were placed into culture, and CD94 expression started 4–6 days after addition of IL-15. Although both CD4+ and CD8+ cells expressed CD94, the simultaneous expression of NKG2A (i.e., the other component of the CD94/NKG2A inhibitory NKR) was confined to CD8+ cells. Similar data were obtained in T cell populations activated in mixed lymphocyte cultures in the presence of IL-15. The expression of CD94/NKG2A led to an impairment of allo-specific cytolytic activity by mixed lymphocyte culture-derived T cell populations or clones. Remarkably, cytolysis could be restored by the addition of anti-CD94 mAb, i.e., by masking the inhibitory NKRs.
National Acad Sciences