Effect of IL-4, IFN-gamma and IL-12 on cytokine production from human CD45RA and CD45RO CD4 T cell precursors.

The aim of this study was to compare the effects of IL-4, IL-12 and IFN-gamma on the production of T helper-1 (Th1) and T helper-2 (Th2)-type cytokines from human peripheral blood 'naive' CD45RA and 'memory' CD45RO CD4 T cells. CD45RA or CD45RO CD4 T cells were cultured for 4 days with phorbol myristate acetate (PMA) and ionomycin and either IL-4, IFN-gamma or IL-12 and their ability to proliferate and secrete IFN-gamma and IL-4 determined. Purified CD45RO CD4 T cells stimulated with PMA and ionomycin secreted higher levels of IL-4 and IFN-gamma, as measured by ELISA, than CD45RA CD4 T cells which secreted little IL-4 or IFN-gamma. However, CD45RA and CD45RO CD4 T cells proliferated to the same extent and IL-4, IFN-gamma and IL-12 had no effect on this. IL-12 and IFN-gamma had no effect on the amount of IL-4 secreted by PMA and ionomycin-stimulated CD45RO CD4 T cells, but culture with IL-4 enhanced IL-4 production 7-fold. IL-12 increased the amount of IFN-gamma produced by CD45RO CD4 T cells 2- to 3-fold. Small amounts of IFN-gamma production were induced in CD4 CD45RA T cells by IL-12 and IFN-gamma. These results indicate: (1) that CD45RA cells cannot make significant amounts of IL-4 under the conditions used, (2) that CD45RO cells can produce both Th1 and Th2 cytokines immediately upon restimulation, (3) that IL-12 favours Th1 cytokine production in both CD45RA and CD45RO CD4 T cells, and (4) that IFN-gamma favours IFN-gamma production in CD45RA but not CD45RO cells.