| First Author | Lee K | Year | 2014 |
| Journal | Am J Transplant | Volume | 14 |
| Issue | 1 | Pages | 27-38 |
| PubMed ID | 24354870 | Mgi Jnum | J:287578 |
| Mgi Id | MGI:6359525 | Doi | 10.1111/ajt.12509 |
| Citation | Lee K, et al. (2014) Attenuation of donor-reactive T cells allows effective control of allograft rejection using regulatory T cell therapy. Am J Transplant 14(1):27-38 |
| abstractText | Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance, suggesting a potential therapeutic role for Tregs in transplantation. However, Treg administration alone is insufficient in inducing long-term allograft survival in normal hosts, likely due to the high frequency of alloreactive T cells. We hypothesized that a targeted reduction of alloreactive T effector cells would allow a therapeutic window for Treg efficacy. Here we show that preconditioning recipient mice with donor-specific transfusion followed by cyclophosphamide treatment deleted 70-80% donor-reactive T cells, but failed to prolong islet allograft survival. However, infusion of either 5 x 10(6) Tregs with direct donor reactivity or 25 x 10(6) polyclonal Tregs led to indefinite survival of BALB/c islets in more than 70% of preconditioned C57BL/6 recipients. Notably, protection of C3H islets in autoimmune nonobese diabetic mice required islet autoantigen-specific Tregs together with polyclonal Tregs. Treg therapy led to significant reduction of CD8(+) T cells and concomitant increase in endogenous Tregs among graft-infiltrating cells early after transplantation. Together, these results demonstrate that reduction of the donor-reactive T cells will be an important component of Treg-based therapies in transplantation. |
