CD8+ T cells produce IL-2, which is required for CD(4+)CD25+ T cell regulation of effector CD8+ T cell development for contact hypersensitivity responses

Interleukin (IL)-2 functions to promote, as well as down-regulate, expansion of antigen-reactive CD4+ and CD8+ T cells, but the role of IL-2 in hapten-specific CD8+ T cell priming for contact hypersensitivity (CHS) responses remains untested. Using enzyme-linked immunospot to enumerate numbers of hapten-specific CD4+ and CD8+ T cells producing IL-2 in hapten-sensitized mice, the number of IL-2-producing CD8+ T cells was tenfold that of CD4+ T cells. Hapten-primed CD4+ T cells produced low amounts of IL-2 during culture with hapten-presenting Langerhans cells, whereas production by hapten-primed CD8+ T cells was fivefold greater. CD8+ T cells did not express CD25 during hapten priming, but treatment with anti-IL-2 or anti-CD25 monoclonal antibodies during hapten sensitization increased hapten-specific effector CD8+ T cells as well as the magnitude and duration of the CHS response. These results indicate that CD8+ T cells are the primary source of IL-2 and that this IL-2 is required for the function of a population of CD(4+)CD25+ T cells to restrict the development of the hapten-reactive effector CD8+ T cells that mediate CHS responses.