Th1 bias and gender differences in the ex vivo functional capacity of human NKT cells. (89.17)

Abstract Human NKT cells are a unique T cell subset capable of producing Th1, Th2, or Th17 cytokines. It is hypothesized that the composite cytokine profile of the NKT cell compartment may determine disease pathogenesis. In order to define the functional signature of individual human NKT cells ex vivo with greater resolution, we FACS-Aria sorted NKT cells from fresh PBMC of 12 healthy donors and assessed their functional profiles, on both a population and single cell level, using Luminex and Elispot platforms, respectively. The purified NKT cell populations produced seven of the 14 analytes measured by Elispot, including IL2, IL4, IFNγ, TNFα, MIP1α, MIP1β, and perforin. Surprisingly, IL5, IL6, IL10, and IL17 were not detected from any subjects, and only one subject’s NKT cells produced IL13. Comparison of Elispot numbers with the distribution of several circulating NKT subsets revealed a significant positive association between the percentage of CD4/CD8 Double Negative cells and the number of perforin-secreting cells. NKT functional profiles of age-matched subjects revealed significantly higher frequencies of Th1-producing cells in male donors. These results suggest that 1) the panoply of human NKT Th2 and Th17 responses may not be as pronounced as previously believed, and 2) NKT cells may contribute to the sex bias found in autoimmune and other diseases.