| First Author | Vu MD | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 1 | Pages | 214-21 |
| PubMed ID | 15210777 | Mgi Jnum | J:90930 |
| Mgi Id | MGI:3045531 | Doi | 10.4049/jimmunol.173.1.214 |
| Citation | Vu MD, et al. (2004) Different costimulatory and growth factor requirements for CD4+ and CD8+ T cell-mediated rejection. J Immunol 173(1):214-21 |
| abstractText | Costimulatory signals and growth factor signals play a key role in commanding T cell activation and T cell effector function. However, how costimulatory signals and growth factor signals interact and integrate into the activation program of CD4(+) and CD8(+) T cells during the allograft response remains poorly defined. In the present study we found that either CD4- or CD8-deficient mice can vigorously reject the skin allografts. Blocking rapamycin-sensitive growth factor signals produced long term skin allograft survival in CD4-deficient mice (mean survival time, >120 days), but not in CD8-deficient mice (mean survival time, 20 days). Analysis of CFSE-labeled cells proliferating in the allogeneic hosts revealed that clonal expansion of CD4(+) T cells in vivo was more resistant to growth factor blockade than that of CD8(+) T cells. However, blockade or genetic absence of CD28/CD154 costimulatory molecules rendered CD4(+) T cell-mediated rejection sensitive to rapamycin, and long term skin allograft survival can be readily induced by rapamycin in the absence of CD28/CD154 signals (>100 days). Furthermore, blocking OX40 costimulation induced long term skin allograft survival in CD4-deficient mice and CD8-deficient mice when both CD28 and CD154 were transiently blocked. We conclude that CD4(+) and CD8(+) T cells exhibit distinct sensitivity to growth factor blockade in transplant rejection, and CD28/CD154-independent rejection is sensitive to rapamycin and appears to be supported by OX40 costimulation. |
