EXPRESSION AND FUNCTION OF THE MADCAM-1 RECEPTOR, INTEGRIN ALPHA-4-BETA-7, ON HUMAN-LEUKOCYTES

Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4(+) T cells th at express high levels of alpha 4 beta 7 migrate selectively to the gu t. We now report that human adult blood CD8(+) T cells and B cells, li ke CD4(+) T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4(+) and CD8() T cell expression of alpha 4 beta 7 was related to age, CD45RA expre ssion, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4(+) and CD8() T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays w ith two alpha 4 beta 7(+) human lymphoma cell lines. The results indic ate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alph a 4 beta 7(+) is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn 2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The abilit y of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expres sion and by the functional state of the alpha 4 beta 7 molecule.