| First Author | Tang Q | Year | 2003 |
| Journal | J Immunol | Volume | 170 |
| Issue | 3 | Pages | 1510-6 |
| PubMed ID | 12538715 | Mgi Jnum | J:126890 |
| Mgi Id | MGI:3762277 | Doi | 10.4049/jimmunol.170.3.1510 |
| Citation | Tang Q, et al. (2003) CD28/B7 regulation of anti-CD3-mediated immunosuppression in vivo. J Immunol 170(3):1510-6 |
| abstractText | FcR-binding 'classical' anti-CD3 mAb is a potent immunosuppressive drug that alters CD4(+) and CD8(+) T cell function in vivo via anergy induction and programmed cell death (PCD). Anti-CD3-mediated PCD was Fas independent but was mediated by the mitochondria-initiated apoptosis that was abrogated in Bcl-x(L)-transgenic T cells. The PCD was more pronounced in CD28-deficient mice consistent with defective Bcl-x(L) up-regulation. Residual T cells isolated from anti-CD3-treated wild-type, CD28(-/-), and Bcl-x(L)-transgenic mice were hyporesponsive. The hyporesponsiveness was more pronounced in CD28(-/-) and wild-type mice treated with anti-B7-2, suggesting that CD28 interaction with B7-2 regulates T cell responsiveness in anti-CD3-treated animals. Finally, anti-CD3 treatment led to indefinite cardiac allograft survival in wild-type but not Bcl-x(L) animals. Together these results implicate CD28/B7 signaling in the regulation of both anti-CD3-induced T cell depletion and hyporesponsiveness in vivo, but T cell depletion, not hyporesponsiveness, appears to be critical for anti-CD3 mAb-mediated long-term immune regulation. |
