| First Author | Murugaiyan G | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 10 | Pages | 6642-9 |
| PubMed ID | 17082576 | Mgi Jnum | J:140499 |
| Mgi Id | MGI:3814000 | Doi | 10.4049/jimmunol.177.10.6642 |
| Citation | Murugaiyan G, et al. (2006) Functional dichotomy in CD40 reciprocally regulates effector T cell functions. J Immunol 177(10):6642-9 |
| abstractText | Activation of T cells requires signals through Ag-specific TCR and costimulatory molecules such as CD40L. Although the use of defined tumor Ags for the induction of protective T cells met with limited success, the CD40-CD40L interaction that was proposed to induce antitumor T cells did not prevent tumor growth completely. Using a model for prostate tumor, a leading cause of tumor-induced mortality in men, we show that the failure is due to a novel functional dichotomy of CD40 whereby it self-limits its antitumor functions by inducing IL-10. IL-10 prevents the CD40-induced CTL and TNF-alpha and IL-12 production, Th1 skewing, and tumor regression. Priming mice with tumor lysate-pulsed IL-10-deficient dendritic cells (DCs) or wild-type DC plus anti-IL-10 Ab establishes antitumor memory T cells that can transfer the protection into syngenic nude mice. Infusion of Ag-pulsed IL-10-deficient but not wild-type DCs back into syngenic mice results in successful therapeutic autovaccination. Thus, we demonstrate the IL-10-sensitive antitumor T cell memory formulating a novel prophylactic and therapeutic principle. |
