Infiltration of a Mesothelioma by IFN-{gamma}-Producing Cells and Tumor Rejection after Depletion of Regulatory T Cells.
J Immunol. 2007 Apr 1;178(7):4089-96
Authors: Rudge G, Barrett SP, Scott B, van Driel IR
Depletion of CD4(+)CD25(+)Foxp3(+) regulatory T cells (CD25(+) T(reg)) with an anti-CD25 Ab results in immune-mediated rejection of tolerogenic solid tumors. In this study, we have examined the immune response to a mesothelioma tumor in mice after depletion of CD25(+) cells to elucidate the cellular mechanisms of CD25(+) T(reg), a subject over which there is currently much conjecture. Tumor rejection was found to be primarily due to the action of CD8(+) T cells, although CD4(+) cells appeared to play some role. Depletion of CD25(+) cells resulted in an accumulation in tumor tissue of CD4(+) and CD8(+) T cells and NK cells that were producing the potent antitumor cytokine IFN-gamma. Invasion of tumors by CD8(+) T cells was partially dependent on the presence of CD4(+) T cells. Although a significant increase in the proliferation and number of tumor-specific CD8(+) T cells was observed in lymph nodes draining the tumor of anti-CD25-treated mice, this effect was relatively modest compared with the large increase in IFN-gamma-producing T cells found in tumor tissue, which suggests that the migration of T cells into tumor tissue may also have been altered. Depletion of CD25(+) cells did not appear to modulate antitumor CTL activity on a per cell basis. Our data suggests that CD25(+) T(reg) limit the accumulation of activated T cells producing IFN-gamma in the tumor tissue and, to a lesser extent, activation and/or rate of mitosis of tumor-specific T cells in lymph nodes.
PMID: 17371963 [PubMed - in process]
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