Interleukin-18 regulates T helper 1 or 2 immune responses of human cord blood CD4+ V alpha 24+V beta 11+ natural killer T cells

Natural killer T (NKT) cells, exhibiting both T-cell and NK-cell markers, are known to regulate immune responses by secreting T-helper (Th) 1 and Th2 cytokines. We analyzed NKT cells in cord blood (CB) for phenotypical and functional characteristics and regulatory mechanisms that control Th1 and Th2 determination. Human CB V alpha 24+V beta 11+ NKT cells were predominantly the CD4+ single positive (SP) phenotype (approximately 96%), in contrast to adult peripheral blood V alpha 24+V beta 11+ NKT cells which are composed of a dominant population of the CD4-CD8-double negative (DN) phenotype and a minor population of the CD4+ SP phenotype. The CB CD4+ V alpha 24+ NKT cells, following stimulation with the primary culture, gained the capacity to secrete interferon (IFN)-gamma, a Th1 cytokine, and interleukin (IL)-13, a Th2 cytokine. The combination of IL-18 and IL-12 induced IFN-gamma production in CB CD4+ V alpha 24+ NKT cells, while IL-18 in combination with IL-2 induced IL-13 production in these cells. Thus, IL-18 regulates the determination of the Th1 or Th2 immune response by human CD4+ V alpha 24+ NKT cells through different cytokine combinations.