| First Author | Kline J | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 6 | Pages | 2630-42 |
| PubMed ID | 22312128 | Mgi Jnum | J:181862 |
| Mgi Id | MGI:5314290 | Doi | 10.4049/jimmunol.1100845 |
| Citation | Kline J, et al. (2012) Cellular and molecular requirements for rejection of b16 melanoma in the setting of regulatory T cell depletion and homeostatic proliferation. J Immunol 188(6):2630-42 |
| abstractText | We have recently demonstrated that adoptive transfer of regulatory T cell-depleted polyclonal T cells into lymphopenic mice leads to rejection of B16 melanoma, which generated an opportunity to study host requirements for tumor rejection when it effectively occurred. CD8(+) T cell priming and tumor rejection required tumor Ag cross-presentation, as evidenced by tumor outgrowth in Kb(-/-) bone marrow chimeric or B71/2(-/-) mice. CD4(+) T cells were additionally required for optimal tumor control, although not through classical CD4 "help," as the frequency of primed CD8(+) T cells was similar in the absence of CD4(+) T cells, and tumor rejection did not depend upon CD40-CD40L interactions or on IL-2 production by CD4(+) T cells. Rather, CD4(+) T cells appeared to act at the effector phase of tumor rejection and responded to B16-derived Ags in vitro. At the effector phase, IFN-gamma production by transferred T cells, but not host cells, was necessary. IFN-gamma acted either on host or tumor cells and was associated with reduced tumor vascularity. Finally, tumor rejection occurred after transfer of TNF-alpha, perforin, or FasL-deficient T cells. However, perforin/FasL double-knockout T cells failed to reject, arguing that the killing of B16 melanoma cells could occur either via the cytotoxic granule or Fas pathways. Collectively, these results support a model in which host tumor Ag cross-presentation primes adoptively transferred T cells, which remain functional in the setting of homeostatic proliferation and regulatory T cell depletion, and which promote tumor rejection via IFN-gamma and lysis via cytotoxic granules and/or FasL. |
