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The Journal of Immunology, 1999, 162: 3256-3262.
Copyright © 1999 by The American Association of Immunologists

Inflammatory Cytokines Provide a Third Signal for Activation of Naive CD4+ and CD8+ T Cells1

Julie M. Curtsinger, Clint S. Schmidt, Anna Mondino, Debra C. Lins, Ross M. Kedl, Marc K. Jenkins and Matthew F. Mescher2

Center for Immunology, University of Minnesota, Minneapolis, MN 55455

The effects of inflammatory cytokines on naive T cells have been studied using MHC protein/peptide complexes on microspheres, thus avoiding the use of APCs whose functions may be affected by the cytokines. IL-1, but not IL-12, increased proliferation of CD4+ T cells in response to Ag and IL-2, which is consistent with effects on in vivo priming of CD4+ cells. In contrast, proliferation of CD8+ T cells to Ag and IL-2 required IL-12, and IL-12 replaced adjuvant in stimulating an in vivo response to peptide. These results support a model in which distinct inflammatory cytokines act directly on naive CD4+ and CD8+ T cells to provide a third signal, along with Ag and IL-2, to optimally activate differentiation and clonal expansion.




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