Mouse TCRαβ+CD8αα intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses

Mouse small intestine intraepithelial lymphocytes (IEL) that express alpha beta TCR and CD8 alpha alpha homodimers are an enigmatic T cell subset, as their specificity and in vivo function remain to be defined. To gain insight into the nature of these cells, we performed global gene expression profiling using microarray analysis combined with real-time quantitative PCR and flow cytometry. Using these methods, TCR alpha beta(+)CD8 alpha alpha IEL were compared with their TCR alpha beta(+)CD8 beta(+) and TCR-gamma delta(+) counterparts. Interestingly, TCR alpha beta(+)CD8 alpha alpha IEL were found to preferentially express genes that would be expected to down-modulate their reactivity. They have a unique expression pattern of members of the Ly49 family of NK receptors and tend to express inhibitory receptors, along with some activating receptors. The signaling machinery of both TCR alpha beta(+)CD8 alpha alpha and TCR-gamma delta(+) IEL is constructed differently than other IEL and peripheral T cells, as evidenced by their low-level expression of the linker for activation of T cells and high expression of the non-T cell activation linker, which suppresses T cell activation. The TCR alpha beta(+)CD8 alpha alpha IEL subset also has increased expression of genes that could be involved in immune regulation, including TGF-beta(3) and lymphocyte activation gene-3. Collectively, these data underscore the fact that, while TCR alpha beta(+)CD8 alpha alpha IEL resemble TCR gamma delta(+) IEL, they are a unique population of cells with regulated Ag reactivity that could have regulatory function.