Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance
Open Access
- 1 September 1997
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 9 (9) , 1355-1365
- https://doi.org/10.1093/intimm/9.9.1355
Abstract
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.Keywords
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