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Interleukin‐12 and interleukin‐2‐induced invariant natural killer T‐cell cytokine secretion and perforin expression independent of T‐cell receptor activation
Author(s) -
Hou Runhua,
Goloubeva Olga,
Neuberg Donna S.,
Strominger Jack L.,
Wilson S. Brian
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01701.x
Subject(s) - perforin , cytotoxic t cell , biology , interleukin 21 , natural killer t cell , cd8 , cytokine , t cell , interleukin 15 , microbiology and biotechnology , t cell receptor , interleukin 3 , immunology , interleukin , immune system , in vitro , biochemistry
Summary Human invariant natural killer (iNK) T cells expressing an invariant Vα24‐Jα15 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‐γ 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.