Effect of IL–4, IFN–Á and IL–12 on Cytokine Production from Human CD45RA and CD45RO CD4 T Cell Precursors

Abstract

The aim of this study was to compare the effects of IL–4, IL–12 and IFN–γ 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–γ or IL–12 and their ability to proliferate and secrete IFN–γ and IL–4 determined. Purified CD45RO CD4 T cells stimulated with PMA and ionomycin secreted higher levels of IL–4 and IFN–γ, as measured by ELISA, than CD45RA CD4 T cells which secreted little IL–4 or IFN–γ. However, CD45RA and CD45RO CD4 T cells proliferated to the same extent and IL–4, IFN–γ and IL–12 had no effect on this. IL–12 and IFN–γ 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–γ produced by CD45RO CD4 T cells 2– to 3–fold. Small amounts of IFN–γ production were induced in CD4 CD45RA T cells by IL–12 and IFN–γ. 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–γ favours IFN–γ production in CD45RA but not CD45RO cells.