| First Author | Martin S | Year | 2010 |
| Journal | J Immunol | Volume | 184 |
| Issue | 10 | Pages | 5510-8 |
| PubMed ID | 20400702 | Mgi Jnum | J:160994 |
| Mgi Id | MGI:4456917 | Doi | 10.4049/jimmunol.0902762 |
| Citation | Martin S, et al. (2010) CD40 signaling in CD8+CD40+ T cells turns on contra-T regulatory cell functions. J Immunol 184(10):5510-8 |
| abstractText | CD4(+) regulatory T cells (Treg cells) mediate immunosuppression, whereas CD8(+) T cells confer resistance in many diseases. It is unknown whether CD8(+) T cells confer protection by antagonizing the Treg cells. Using a model of stage-specific immune responses against Leishmania donovani infection in susceptible BALB/c mice, we report that CD3(+)CD8(+)CD40(+) T cells executed CD40-dependent cytotoxicity on CD3(+)CD4(+)CD127(dim)GITR(+)CD25(+) Treg cells during the initial phase of the infection but were later apoptosed by IL-10. CD40 signaled through Ras, PI3K, and protein kinase C, resulting in p38MAPK- or ERK-1/2-independent, but NF-kappaB-dependent, induction of the cytotoxic mediators granzyme and perforin. Adoptive transfer of CD3(+)CD8(+)CD40(+) T cells reduced the L. donovani infection in BALB/c mice. These results identify CD3(+)CD8(+)CD40(+) T cells as the contra-Treg cells and imply a novel immunotherapeutic principle. |
