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.
Wilson
Elizabeth B
EB
Department of Microbiology and Immunology, David H Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences and University of Rochester Medical Center, Rochester, NY 14642, USA.
Livingstone
Alexandra M
AM
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000941:Antigens; C508018:Il2ra protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand