| First Author | van Meerwijk JP | Year | 1999 |
| Journal | Blood | Volume | 93 |
| Issue | 11 | Pages | 3856-62 |
| PubMed ID | 10339493 | Mgi Jnum | J:55385 |
| Mgi Id | MGI:1337885 | Doi | 10.1182/blood.v93.11.3856.411k26_3856_3862 |
| Citation | van Meerwijk JP, et al. (1999) In vivo T-lymphocyte tolerance in the absence of thymic clonal deletion mediated by hematopoietic cells. Blood 93(11):3856-62 |
| abstractText | Thymic negative selection renders the developing T-cell repertoire tolerant to self-major histocompatability complex (MHC)/peptide ligands. The major mechanism of induction of self-tolerance is thought to be thymic clonal deletion, ie, the induction of apoptotic cell death in thymocytes expressing a self-reactive T-cell receptor. Consistent with this hypothesis, in mice deficient in thymic clonal deletion mediated by cells of hematopoietic origin, a twofold to threefold increased generation of mature thymocytes has been observed. Here we describe the analysis of the specificity of T lymphocytes developing in the absence of clonal deletion mediated by hematopoietic cells. In vitro, targets expressing syngeneic MHC were readily lysed by activated CD8(+) T cells from deletion-deficient mice. However, proliferative responses of T cells from these mice on activation with syngeneic antigen presenting cells were rather poor. In vivo, deletion-deficient T cells were incapable of induction of lethal graft-versus-host disease in syngeneic hosts. These data indicate that in the absence of thymic deletion mediated by hematopoietic cells functional T-cell tolerance can be induced by nonhematopoietic cells in the thymus. Moreover, our results emphasize the redundancy in thymic negative selection mechanisms. |
