RT Journal Article SR Electronic T1 CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 2591 OP 2601 DO 10.4049/jimmunol.174.5.2591 VO 174 IS 5 A1 Antony, Paul A. A1 Piccirillo, Ciriaco A. A1 Akpinarli, Akgül A1 Finkelstein, Steven E. A1 Speiss, Paul J. A1 Surman, Deborah R. A1 Palmer, Douglas C. A1 Chan, Chi-Chao A1 Klebanoff, Christopher A. A1 Overwijk, Willem W. A1 Rosenberg, Steven A. A1 Restifo, Nicholas P. YR 2005 UL http://www.jimmunol.org/content/174/5/2591.abstract AB CD4+ T cells control the effector function, memory, and maintenance of CD8+ T cells. Paradoxically, we found that absence of CD4+ T cells enhanced adoptive immunotherapy of cancer when using CD8+ T cells directed against a persisting tumor/self-Ag. However, adoptive transfer of CD4+CD25− Th cells (Th cells) with tumor/self-reactive CD8+ T cells and vaccination into CD4+ T cell-deficient hosts induced autoimmunity and regression of established melanoma. Transfer of CD4+ T cells that contained a mixture of Th and CD4+CD25+ T regulatory cells (Treg cells) or Treg cells alone prevented effective adoptive immunotherapy. Maintenance of CD8+ T cell numbers and function was dependent on Th cells that were capable of IL-2 production because therapy failed when Th cells were derived from IL-2−/− mice. These findings reveal that Th cells can help break tolerance to a persisting self-Ag and treat established tumors through an IL-2-dependent mechanism, but requires simultaneous absence of naturally occurring Treg cells to be effective.