Comparative effects of interleukin-12 and interleukin-4 on cytokine responses by antigen-stimulated memory CD4(+) T cells of cattle: IL-12 enhances IFN-gamma production, whereas IL-4 has marginal effects on cytokine expression

Interleukin-12 (IL-12) and IL-4 are important immunoregulatory cytokines th at determine the fate of naive T cells during antigen priming in mice and a lso influence cytokine synthesis by differentiated murine and human T cells . The roles of these cytokines in regulating the differentiation and effect or function of bovine T cells are less well studied. We investigated the ab ility of human IL-12 and bovine IL-4 to modify cytokine expression by antig en-stimulated T cells from cattle immune to the protozoal parasites Babesia bovis and Babesia bigemina or reactive with Mycobacterium bovis purified p rotein derivative. Peripheral blood mononuclear cells (PBMC) were cultured with specific antigen and IL-4 or IL-12 for 1 week. Then viable lymphoblast s consisting of predominantly CD4(+) T cells were restimulated with antigen and antigen-presenting cells (APC) with or without cytokine. Cell lines we re cultured for several weeks, and following restimulation with antigen and APC in the absence of exogenous cytokine, the cell lines were analyzed for proliferation, interferon-gamma (IFN-gamma) production, and expression of IL-2, IL4-, IL-10, or IFN-gamma transcript levels using a quantitative comp etitive RT-PCR. IL-12 and IL-4 had no effect on the composition of CD4, CD8 , or gamma delta T cells in the cell lines or on the level of antigen-induc ed proliferation. IL-12 stimulated enhanced levels of IFN-gamma protein and transcript expression in all cell lines, with no consistent effects on IL- 2 or IL-4 expression. In two B. bovis-specific cell lines, IL-12 suppressed IL-10 expression. IL-4 had no consistent effect on expression of any cytok ine. These results indicate the use of IL-12 as an adjuvant to enhance type 1 cytokine responses in cattle during antigen priming.