Expression of activation and costimulatory elements by human intestinal intraepithelial lymphocytes

It is unclear whether human intestinal intraepithelial T lymphocytes (iIEL) are resting or activated cells. To address this question, an improved isol ation procedure was developed for small bowel iIEL, which were analysed by two-colour flow cytometry and compared with resting and mitogen-activated p eripheral blood lymphocytes. iIEL expression of CD44 isoforms, Bcl-2 and Ki 67 antigen was also determined in tissue sections, iIEL expressed CD69 at l evels comparable with 48-72 h phytohaemagglutinin blasts, but did not expre ss CD25 or CD95. iIEL were Bcl-2(+) but not Ki67(+). alpha E beta 7 and alp ha 4B7 expression was relatively high, whereas alpha L beta 2, CD5 and CD28 were expressed at low density. Isolated iIEL expressed CD44 (core epitopes ) at lower levels than peripheral blood lymphocytes, although almost all CD 44 contained splice variant 6 (CD44v6). Peripheral blood lymphocytes expres sed CD44 at very high density, but little CD44V6, even after activation. Ho wever, in tissue sections, iIEL showed differential labelling with CD44 cor e epitope antibodies and no detectable CD44v6, implying CD44 receptor occup ancy or epitope masking in situ. Thus, normal iIEL express a quasi-activate d phenotype with unusual patterns of adhesion receptors, which may act as c ostimulatory elements. These may permit iIEL to assume effector functions, with absence of CD25 preventing entry into the cell cycle, thereby maintain ing an apoptosis-resistant phenotype.