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The human intestine contains two populations of anatomically distinct T cells, intraepithelial lymphocytes and lamina propria lymphocytes (LPLs), both of which preferentially use the TCR-alpha beta. Recent studies of TCR alpha- and beta-chain usage by intestinal intraepithelial lymphocytes, which are predominantly CD8+ T cells, have demonstrated that these cells are oligoclonal in normal intestine. This report examined the TCR beta-chains expressed by purified CD4+ and CD8+ T cells from normal colonic lamina propria and from the intestinal mucosa of patients with active ulcerative colitis (UC). The selective expansion of CD8+ T cell clones, and to a lesser extent CD4+ T cell clones, was observed among both normal LPLs and mucosal T cells in UC. These expanded LPL clones from normal donors were all distinct, but the mucosal T cells isolated from five of nine patients with UC contained CD8+ T cells expressing related V beta 3-J beta 1.6 TCRs. These observations provide evidence for an Ag-specific mucosal T cell response in UC. Further studies will be required to identify this Ag and address whether the T cell response to it plays a primary role in initiating the disease or is secondary to the inflammatory response.

The majority of human intestinal intraepithelial lymphocytes (iIELs) are CD8+ T cells that use the T cell receptor (TCR)-alpha/beta. Previous studies have shown that iIELs isolated from segments of small intestine or colon contain one or several dominant alpha/beta T cell clones. It is not known whether these clones expand only locally in response to a particular antigen or whether they are widely distributed throughout the intestine. To address this question, iIELs were purified from near the proximal and distal margins in a series of intestinal resections for noninflammatory diseases. TCR-beta expression was then assessed by semiquantitative polymerase chain reaction amplification, analysis of N-region length, and DNA sequencing. The previously described oligoclonal expansion of iIELs was confirmed in each sample. Identical dominant clones were identified in the proximal and distal samples from most cases, including samples taken from sites as distant as the transverse and sigmoid colon or rectum. Distinct clones were found in only one case with samples from the terminal ileum and transverse colon. These results demonstrate that a relatively small number of widely dispersed T cell clones comprise the majority of cells in the human intestinal mucosa.

Intestinal intraepithelial lymphocytes (IEL) are a phenotypically distinct T cell population of unknown function. The majority of human intestinal IEL express the TCR-alpha beta, 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 by these cells have shown marked skewing toward one or several V region genes in individual donors and revealed the presence of clonally expanded cells. In addition, functional data has suggested that the MHC class I-like CD1 molecules may be the target ligands for some human intestinal IEL clones. This report examines in detail the TCR-beta repertoire of human jejunal IEL to determine what fraction of these cells are clonally expanded and to determine whether a particular subset of V beta genes are utilized by the clonally expanded cells. The results demonstrate that the majority of IEL are derived from the expansion of a relatively few T cell clones and that these clones can utilize a large number of different V beta genes. Oligoclonal expansion is also demonstrated among lamina propria lymphocytes (LPL), with overlapping but distinct clones detected in the LPL vs the IEL populations. These results indicate that most intestinal IEL-alpha beta, and a subpopulation of LPL, are specific for a limited number of Ag and place constraints on the possible roles played by IEL in the defense against diverse environmental pathogens or in the generation of oral tolerance.