CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells (original) (raw)

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 (T reg cells) or T reg 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 T reg cells to be effective.