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

Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1172-7. doi: 10.1073/pnas.95.3.1172.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis*
  • Antigens, CD / immunology
  • Bacterial Toxins*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Clone Cells
  • Enterotoxins / pharmacology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Interleukin-15 / pharmacology*
  • Isoantigens / immunology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / immunology
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic / biosynthesis*
  • Receptors, Immunologic / immunology
  • Receptors, Mitogen / biosynthesis*
  • Receptors, Mitogen / immunology
  • Receptors, Mitogen / metabolism
  • Receptors, Natural Killer Cell
  • Staphylococcus aureus
  • Superantigens / immunology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, CD
  • Bacterial Toxins
  • Enterotoxins
  • Histocompatibility Antigens Class I
  • Interleukin-15
  • Isoantigens
  • KLRC1 protein, human
  • KLRD1 protein, human
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Immunologic
  • Receptors, Mitogen
  • Receptors, Natural Killer Cell
  • Superantigens
  • enterotoxin F, Staphylococcal