| First Author | Brennan TV | Year | 2011 |
| Journal | J Surg Res | Volume | 169 |
| Issue | 1 | Pages | e69-75 |
| PubMed ID | 21571317 | Mgi Jnum | J:278583 |
| Mgi Id | MGI:6358898 | Doi | 10.1016/j.jss.2011.03.021 |
| Citation | Brennan TV, et al. (2011) Requirements for prolongation of allograft survival with regulatory T cell infusion in lymphosufficient hosts. J Surg Res 169(1):e69-75 |
| abstractText | BACKGROUND: For the clinical applicability of regulatory T cells (Tregs) in transplantation, it is critical to determine if donor antigen specificity is required for their immunosuppressive function. We developed an allospecific CD4(+) T cell receptor transgenic (TCR-tg) mouse as a source for large numbers of Tregs with defined allospecificity and tested whether they are more effective than polyclonal Tregs at suppressing allograft rejection. MATERIALS AND METHODS: CD4(+)CD25(+)CD62L(hi) T cells were sorted from the spleen and peripheral lymph nodes of wild-type (WT-Tregs) and TCR-tg (Allo-Tregs) mice, and expanded using IL-2 and anti-CD3/anti-CD28 conjugated magnetic beads. Tregs were tested for their ability to suppress the proliferation and cytokine production of alloreactive CD4(+)CD25(-) T cells in mixed leukocyte assays. Syngeneic WT hosts were adoptively transferred 5 x 10(6) Tregs and transplanted with allogeneic hearts. RESULTS: Using anti-CD3/anti-CD28 conjugated beads, Tregs were expanded in vitro 100-fold and maintained their suppressor phenotype and function. Allo-Tregs were 6-8 times more potent on a cell-for-cell basis than WT-Tregs in suppressing allospecific proliferation in vitro. Allo-Tregs were unable to suppress in the absence of allo-antigen. Adoptive transfer of expanded Allo-Tregs into WT recipients prolonged the graft survival in a F1 heart transplant model compared with WT-Treg or no treatment [20.0 +/- 4.4 d (n = 6) versus 10.4 +/- 1.2 (n = 8) and 9.7 +/- 1.6 d (n = 6)]. CONCLUSIONS: Unlike polyclonal Tregs, allospecific Tregs are able to prolong allograft survival. However, large numbers of Allo-Tregs were unable to induce tolerance, suggesting that Treg therapy in immunocompetent recipients will require conditioning and/or additional immunomodulation for the induction of tolerance. |
