Journal
AUTOIMMUNITY
Volume 37, Issue 8, Pages 537-547Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/08916930400027094
Keywords
mucosa; T cells; MHC; transgenic/knockout mice; cell differentiation
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Funding
- NIAID NIH HHS [AI 44990] Funding Source: Medline
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The intestinal epithelium is unique in that it harbors auto- reactive T cells largely absent from the peripheral TCR repertoire in normal mice. Intestinal intraepithelial lymphocytes ( IEL) expressing self- reactive TCR are mostly CD8 alpha alpha(+) cells in adult H- Y TCR RAG (-/-) male mice homozygous for the restricting MHC I allele, H-2D (b). By contrast, in male mice heterozygous for the restricting and non- restricting MHC I allele, H-2D (d) ( MHC F-1, H- 2D (b/d)), IEL are composed of CD8 alpha beta and CD8 alpha alpha(+) T cells. Here we demonstrate that IEL in the immediate postnatal period of MHC homozygous male mice were mostly CD8(-) T cells, while IEL in MHCF1 male mice were CD8(-) andCD8 alpha beta(+) Tcells. Regardless of the MHC I configuration and the ability to support positive selection of CD8 alpha beta(+) cells in the thymus, the expansion of CD8 alpha alpha(+) IEL was a late postnatal event that followed a reduction in CD8(-) IEL. Furthermore, although in vivo treatment with the specific peptide antigen resulted in an earlier accumulation of activated IEL, the expansion of CD8 alpha alpha(+) IEL remained inefficient until late in postnatal life. Finally, as CD8(-) IEL stimulated with TCR agonists in vitro, acquired expression of CD8 alpha alpha, we propose that CD8 alpha alpha(+) IEL derive from CD8(-) IEL intermediates. Whether CD8(-) IEL are CD8 alpha beta- lineage cells that escape deletion in the thymus or are T cells targeted to the intestine from the thymus because of the early and high level TCR transgene expression in this model, is not clear. The signals required for the expansion of CD8 alpha alpha(+) IEL are however, incomplete in the immediate postnatal intestine. Determining the factors required for the expansion or retention of CD8 alpha alpha(+) IEL bearing high affinity, self- specific TCR will further elucidate the in vivo role of these T cells in intestinal homeostasis and perhaps, autoimmunity.
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