Similar co-stimulation requirements of CD4+ and CD8+ primary T helper cells: role of IL-1 and IL-6 in inducing IL-2 secretion and subsequent proliferation

Abstract

Primary murine CD4⁺ and CD8⁺ T helper (Th) cells provide help for various immune responses by secreting lymphokines which activate effector cells. The purpose of the present study was to investigate the co-stimulatory signals that, together with T cell receptor (TCR) cross-linking, induce phentypically distinct primary Th cells to secrete IL-2 and proliferate. We isolated highly purified populations of primary CD4⁺ or CD8⁺ T cells and stimulated them in vitro with plate-bound anti-CD3 mAb. TCR cross-linking by anti-CD3 mAb induced both IL-2 receptor expression and responsiveness to exogenous IL-2, but was not sufficient to induce either IL-2 secretion or T cell proliferation. Rather, for both CD4⁺ and CD8⁺ primary Th cells, IL-2 secretion and proliferation required both TCR cross-linking and antigen presenting cell (APC)-derived co-stimulatory signals. Based on G-10 adherence and sensitivity to γ-irradiation, the APC populations able to induce primary CD4⁺ Th cells and primary CD8⁺ Th cells to secrete IL-2 were indistinguishable. In addition, we found that either IL-1 or IL-6 could replace the requirement for APC-derived co-stimulatory signals for IL-2 secretion and proliferation by both primary CD4⁺ Th cells and primary CD8⁺ Th cells. Thus, the present study has examined and compared the co-stimulatory requirements of rigorously purified subsets of IL-2-secretlng primary CD4⁺ and primary CD8⁺ T cells. We conclude that the co-stimulatory requirements for IL-2 secretion by primary CD4⁺ and CD8⁺ Th cells share many similarities, and that they differ significantly from the reported co-stimulatory requirements of antigen-primed IL-2-secreting CD4⁺ Th cell clones.