Differential proliferative response of NKT cell subpopulations in vitro stimulations in presence of different cytokines

Abstract

Human Vα24+Vβ11+ NKT (NKT) cells have immune regulatory activities associated with rejection of tumors, infections and control of autoimmune diseases. They can be stimulated to proliferate using α-galactosylceramide (KRN7000) and have the potential for therapeutic manipulation. Subpopulations of NKT cells (CD4+CD8-, CD4-CD8+ and CD4-CD8-) have functionally distinctive Th1/Th2 cytokine profiles and their relative numbers following stimulation may influence the Th1/Th2 balance, which may result in or prevent disease, We aimed to determine the effect of different cytokines in culture during stimulation of NKT cells on the relative proportions of NKT cell subpopulations. Our results show that all NKTcell subpopulations expanded following stimulation with KRN7000 and IL-2, IL-7, IL-12 or IL-15. Expansion capacity differed between subpopulations, resulting in different relative proportions of CD4+ and CD4- NKTcell subpopulations, and this was influenced by the cytokine used for stimulation. A Th1-biased environment was observed after stimulation of NKTcells. NKTcells expanded under all conditions evaluated demonstrated significant cytotoxicity against U937 tumor cells. In view of the potential for NKT cell subsets to alter the balance of Th1 and Th2 environment, these data provide insights into the effects of NKT cell manipulation for possible therapeutic applications in different disease settings. © 2004 Wiley-VCH Verlag GmbH & Co.