Journal
JOURNAL OF IMMUNOLOGY
Volume 183, Issue 12, Pages 7656-7660Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0902625
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Funding
- National Institutes of Health [R01-CA100656-01A1]
- New York State Office of Science Technology and Academic Research (NYSTAR) [C040070]
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Tumor-resident CD8(+) T cells display a quiescent effector/memory phenotype that is maintained in part by infiltrating CD4(+) CD25(+) Foxp3(+) T-suppressor cells. Intratumoral delivery of IL-12, in contrast, can restore cytotoxic function to tumor-associated CD8(+) T cells and induce the apoptotic death of T-suppressor cells. Depletion of CD8(+) T cells from tumors before IL-12 treatment resulted in the abrogation of treatment-mediated T-suppressor cell apoptosis revealing a link between CD8(+) T cell activation and T-suppressor elimination. Furthermore, IL-12 failed to induce T-suppressor cell loss in IFN-gamma- or FasL-deficient mice demonstrating a requirement for IFN-gamma and FasL in this process. Adoptive transfer of wild-type CD8(+) T cells to FasL-knockout mice restored posttherapy T-suppressor cell elimination from tumors establishing that expression of FasL on CD8(+) T cells was sufficient to promote T-suppressor cell death. IL-12 failed to induce FasL on T-effectors in IFN-gamma-knockout mice demonstrating a requirement for IFN-gamma in FasL up-regulation. Adoptive transfer of wild-type CD8(+) T cells induced T-suppressor cell death in IFN-gamma-knockout mice confirming that autocrine IFN-gamma was sufficient for CD8(+) T cell FasL expression. These findings reveal a mechanism by which cytotoxic T cells can abrogate regulatory cell activity. The Journal of Immunology, 2009, 183: 7656-7660.
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