RT Journal Article
SR Electronic
T1 CD8<sup>+</sup> T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4<sup>+</sup> 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.