| First Author | Yang L | Year | 1998 |
| Journal | Blood | Volume | 91 |
| Issue | 1 | Pages | 324-30 |
| PubMed ID | 9414301 | Mgi Jnum | J:45070 |
| Mgi Id | MGI:1101687 | Doi | 10.1182/blood.v91.1.324.324_324_330 |
| Citation | Yang L, et al. (1998) Mechanisms of long-term donor-specific allograft survival induced by pretransplant infusion of lymphocytes. Blood 91(1):324-30 |
| abstractText | Pretransplantation donor-specific transfusion (DST) can enhance allograft survival in man and animals. However, due to the lack of a specific marker to identify donor-reactive cells in vivo in man and normal (nontransgenic) animals, the underlying mechanism remains unknown. In this study, we use 2CF1 transgenic mice expressing a transgenic T-cell receptor (TCR) specifically recognizing Ld, a major histocompatibility complex (MHC) class I molecule, to delineate the role of DST in long-term skin allograft survival and its underlying mechanisms. Our main findings include: (1) in the absence of any other immunosuppressive treatment, a single dose pretransplantation infusion of viable splenocytes from an Ld+ donor is sufficient to induce permanent donor-specific skin allograft survival in 2CF1 anti-Ld TCR transgenic mice; (2) DST leads to a deletion of the majority (>60%) of donor-reactive T cells in the periphery of the recipient. However, deletion does not necessarily result in tolerance; (3) remaining donor-reactive T cells from DST-treated mice are fully responsive to Ld in vitro, and can suppress the antidonor response of naive T cells in vitro only when exogenous interleukin (IL)-4 is provided; and (4) the sera level of IL-4 in DST-treated tolerant mice is significantly increased. These results suggest that the generation of a subset of T cells with the potential to specifically inhibit antidonor responses, together with promotion of IL-4 production in recipients, may be important mechanisms for the induction and maintenance of antigen- specific tolerance. |
