Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses.

CD4(+) T cell help is essential for primary CD8(+) T cell responses to noninflammatory Ags. IL-2 is one of the principal cytokines made by naive CD4(+) T cells, and we show in this study that it is an essential component of help. Adoptively transferred naive CD4(+) TCR-transgenic OT-II cells supported endogenous primary CD8(+) T cell responses, but IL-2-deficient OT-II cells were unable to provide help, although they responded to Ag in vivo and up-regulated CD40 ligand in vitro. Wild -type OT-II cells helped endogenous CD8(+) T cell responses in IL-2-deficient mice, but not in IL-2Ralpha-deficient mice. Thus, CD4(+) T cell-derived IL-2 is essential for CD8(+) T cell responses to noninflammatory, cell-associated Ags. We suggest that it is also a critical component of help for CD8(+) T cell responses to pathogens, because protective memory also requires CD8(+) T cell stimulation by IL-2 during priming.