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 Vα24+Vβ11+ NKT cells were predominantly the CD4+ single positive (SP) phenotype (approximately 96%), in contrast to adult peripheral blood Vα24+Vβ11+ 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+ Vα24+ NKT cells, following stimulation with the primary culture, gained the capacity to secrete interferon (IFN)-γ, a Th1 cytokine, and interleukin (IL)-13, a Th2 cytokine. The combination of IL-18 and IL-12 induced IFN-γ production in CB CD4+ Vα24+ 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+ Vα24+ NKT cells through different cytokine combinations.

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