INTERLEUKIN-4 AND INTERFERON-GAMMA REGULATE DIFFERENTIATION OF CD8(-CELLS INTO POPULATIONS WITH DIVERGENT CYTOKINE PROFILES() T)

The ability of CD8(+) T cells to synthesise and secrete cytokines befo re and after culture with interleukin (IL)-4 and anti-interferon (IFN) -gamma was investigated. Purified rat splenic CD8(+) and CD4(+) T cell s and CD4(-)CD8(-) cells were stimulated with phorbol myristate acetat e (PMA) and ionomycin for 6 h and expression of mRNA for IL-2, IL-4, I L-5, IL-6, IL-10 and IFN-gamma determined using a quantitative PCR tec hnique. Secreted IFN-gamma and IL-2 were measured by ELISA and bioassa y, respectively, 24 h after restimulation. The highest levels of IL-4, IL-5 and IFN-gamma, mRNA were expressed by CD8(+) T cells, the highes t levels of message for IL-2 were expressed by CD4(+) T cells and the highest levels of message for IL-6 and IL-10 by CD4(-)CD8(-) splenocyt es. Purified rat splenic CD8(+) T cells were cultured for 6 days with PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma, and re stimulated with PMA and ionomycin. Those CD8(+) T cells cultured with IL-4 expressed increased levels of IL-4, IL-5 and reduced levels of IL -2 and IL-6 mRNA, while CD8(+) T cells cultured with IL-4 and anti-IFN -gamma expressed increased levels of mRNA for IL-10 and IFN-gamma. Com parable effects were seen for secreted IFN-gamma and IL-2. These resul ts indicate that CD8(+) T cells have the potential to produce large am ounts of Th2 cytokines and are able to differentiate into different su bpopulations with distinct cytokine profiles under the control of IL-4 and IFN-gamma.