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David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences and Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642
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-2R
-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.
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1 This work was supported by National Institutes of Health (NIH) Grant AI48721 (to A.M.L.) and NIH Training Grant AI007285 (to E.B.W.).
2 Address correspondence and reprint requests to Dr. Alexandra Livingstone, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 609, Rochester NY 14642. E-mail address: alexandra_livingstone{at}urmc.rochester.edu
3 Abbreviations used in this paper: CD40L, CD40 ligand; B6, C57BL/6 mice; DC, dendritic cell; KLH, keyhole limpet hemocyanin; pOVAI, Kb-restricted OVA257–264 peptide; pOVAII, I-Ab-restricted OVA323–339 peptide; pTRP2I, Kb-restricted tyrosinase-related protein-2 (TRP2180–188) peptide; WT, wild type.
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