The TCR-beta chain repertoire of gut-derived T lymphocytes

The gastrointestinal tract represents a natural barrier to environmental pathogens. The gut-associated lymphoid tissue (GALT) provides protection and interacts with the external environment, e.g. bacteria and food antigens. Large numbers of leukocytes are present as aggregates in the lymphoid follicles and as single cells in the lamina propria and epithelium. Intraepithelial T lymphocytes are localized within the tight junctions between epithelial cells. In conventional adult mice, they mainly express CD8, with half of the cells expressing the common CD8 molecule, the CD8 alpha beta heterodimer and the other half expressing a homodimer CD8 alpha alpha. The CD8 alpha beta IEL bear a TcR alpha beta while CD8 alpha alpha bear either a TcR gamma delta or a TcR alpha beta. Studies of repertoire with human IEL cell lines and with total human IEL population showed that both the alpha-chain and the beta-chain repertories are oligoclonal. Our own results of the analysis of repertoire diversity in genetically identical mice raised the same environment have shown that both CD8 alpha alpha and CD8 alpha beta TcR alpha beta IEL populations express a distinct oligoclonal repertoire that differs from one individual to the next. Compared to the lymph node lymphocytes, both IEL populations are composed of a very limited number of clones that undergo clonal expansion. Furthermore, the study of repertoire throughout the length of the small intestine has revealed that some of the clones are present all along the epithelium suggesting that the CD8 alpha alpha IEL and CD8 alpha beta IEL are capable of recirculating or migrating in the intestine. We propose that the repertoire of TcR alpha beta IEL is derived from a restricted number of T cells that either develop in situ or that arrive through circulation and can then undergo clonal expansion.