Interleukin‐12 and interleukin‐2‐induced invariant natural killer T‐cell cytokine secretion and perforin expression independent of T‐cell receptor activation

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Abstract
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.