Natural killer activating receptors trigger interferon gamma secretion from T cells and natural killer cells.
Proliferation of human CD4+ alphabeta T cells expressing a natural killer cell activating receptor (NKAR) has been shown to be enhanced, particularly in response to low doses of antigen, if the target cells present appropriate human class I major histocompatibility complex (MHC) molecules. Here, we show that NKAR also enhance proliferation and killing of target cells by subsets of CD8+ alphabeta and CD8+ gammadelta T cells, as well as by NK cells. Strikingly, interferon gamma secretion from all of these types of lymphocytes was markedly increased by interaction of the NKAR with their MHC class I ligands, independently of enhancement of proliferation. Thus, the recognition of class I MHC molecules by NKAR on both T cells and NK cells may provide a regulatory mechanism that affects immune responses through the secretion of interferon gamma and possibly other cytokines. It represents a signal for cytokine secretion alternative and/or augmentative to that through the T cell receptor.
Mandelboim
O
O
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 01238, USA.
Kent
S
S
Davis
D M
DM
Wilson
S B
SB
Okazaki
T
T
Jackson
R
R
Hafler
D
D
Strominger
J L
JL
D019002:CD56 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D019002:CD56 Antigen; D015395:Histocompatibility Antigens Class I; C081849:NKTR protein, human; D011971:Receptors, Immunologic; D007371:Interferon-gamma