Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 5, Pages 2591-2601Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.5.2591
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- Intramural NIH HHS [Z01 BC010763-01, Z01 SC003811-32, Z99 CA999999] Funding Source: Medline
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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.
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