HUMAN INTESTINAL INTRAEPITHELIAL LYMPHOCYTES ARE DERIVED FROM A LIMITED NUMBER OF T-CELL CLONES THAT UTILIZE MULTIPLE V-BETA T-CELL RECEPTOR GENES

Intestinal intraepithelial lymphocytes (IEL) are a phenotypically dist inct T cell population of unknown function. The majority of human inte stinal IEL express the TCR-alphabeta, the CD8 accessory molecule, and the CD45RO Ag, suggesting that they are MHC class I-restricted memory T cells. Recent analyses of the TCR alpha- and beta-chains expressed b y these cells have shown marked skewing toward one or several V region genes in individual donors and revealed the presence of clonally expa nded cells. In addition, functional data has suggested that the MHC cl ass I-like CD1 molecules may be the target ligands for some human inte stinal IEL clones. This report examines in detail the TCR-beta reperto ire of human jejunal IEL to determine what fraction of these cells are clonally expanded and to determine whether a particular subset of Vbe ta genes are utilized by the clonally expanded cells. The results demo nstrate that the majority of IEL are derived from the expansion of a r elatively few T cell clones and that these clones can utilize a large number of different Vbeta genes. Oligoclonal expansion is also demonst rated among lamina propria lymphocytes (LPL), with overlapping but dis tinct clones detected in the LPL vs the IEL populations. These results indicate that most intestinal IEL-alphabeta, and a subpopulation of L PL, are specific for a limited number of Ag and place constraints on t he possible roles played by IEL in the defense against diverse environ mental pathogens or in the generation of oral tolerance.