Interleukin-12 and interleukin-2-induced invariant natural killer T-cell cytokine secretion and perforin expression independent of T-cell receptor activation.
Human invariant natural killer (iNK) T cells expressing an invariant Valpha24-Jalpha15 T-cell receptor (TCR) are thought to be important regulators of autoimmunity and tumour surveillance. Two major subsets of iNK T cells, CD4+ or CD4- CD8- are known to exist, but the in vivo importance of CD4 expression is unclear. Since interleukin-12 (IL-12) is a key iNK T-cell-activating cytokine, the effect of IL-12 plus or minus the T-cell growth factor IL-2 on a large panel of CD4+ versus CD4- CD8- iNK T-cell clones was examined. Strikingly, IL-12 and IL-2 significantly activated iNK T cells to secrete IL-4, interferon-gamma and granulocyte-macrophage colony-stimulating factor, and up-regulated perforin expression in the absence of TCR stimulation. Furthermore, IL-2 and IL-12 treatment resulted in a preferential increase in apoptosis of CD4- CD8- clones. Thus, independent of TCR activation, IL-2 and IL-12 can directly activate iNK T cells and provide a selective advantage to the CD4+ iNK T-cell population.
Hou
Runhua
R
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Goloubeva
Olga
O
Neuberg
Donna S
DS
Strominger
Jack L
JL
Wilson
S Brian
SB
D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; D018664:Interleukin-12