| First Author | Smith KM | Year | 1997 |
| Journal | Int Immunol | Volume | 9 |
| Issue | 9 | Pages | 1355-65 |
| PubMed ID | 9310839 | Mgi Jnum | J:44775 |
| Mgi Id | MGI:1101289 | Doi | 10.1093/intimm/9.9.1355 |
| Citation | Smith KM, et al. (1997) Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance. Int Immunol 9(9):1355-65 |
| abstractText | We report the initial characterization of rare cells within the thymus that express 'peripheral' self-antigens and are capable of inducing partial tolerance to a model protein. Mice from two transgenic families that express SV40 T antigen (Tag) in pancreatic islet beta cells under control of a rat insulin promoter (RIP) develop T cell tolerance toward this neo-self antigen. These mice express low levels of Tag mRNA in the thymus. Transplantation of thymus from tolerant RIP-Tag mice into athymic hosts is sufficient to confer tolerance by CD4+ Th cells and elicits variable tolerance by CD8+ cytotoxic T cells. Thymic medulla is shown to contain rare cells that express the endogenous insulin and somatostatin genes, and in the transgenic animals, Tag. These cells are referred to as 'peripheral antigen-expressing' (PAE) cells. Thymic cell fractionation reveals the PAE cells expressing insulin and Tag to be present in a fraction enriched for non-lymphoid, MHC class II+ cells. Notably, absence of thymic expression of the RIP-Tag gene in another transgenic family correlates with failure to establish self-tolerance and susceptibility to autoimmunity. Thus, expression of tissue-restricted genes such as insulin in PAE cells of thymic medulla may serve to limit development of potentially autoimmune T cells. |
