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Geordie Rudge, Simon P Barrett, Bernadette Scott, Ian R van Driel, Infiltration of a Mesothelioma by IFN-γ-Producing Cells and Tumor Rejection after Depletion of Regulatory T Cells, The Journal of Immunology, Volume 178, Issue 7, April 2007, Pages 4089–4096, https://doi.org/10.4049/jimmunol.178.7.4089
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Abstract
Depletion of CD4+CD25+Foxp3+ regulatory T cells (CD25+ Treg) 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+ Treg, 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-γ. 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-γ-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+ Treg limit the accumulation of activated T cells producing IFN-γ in the tumor tissue and, to a lesser extent, activation and/or rate of mitosis of tumor-specific T cells in lymph nodes.
