Erle D J, Briskin M J, Butcher E C, Garcia-Pardo A, Lazarovits A I, Tidswell M
Department of Medicine, University of California, San Francisco 94143.
J Immunol. 1994 Jul 15;153(2):517-28.
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 that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like 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 expression, 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 with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability 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 expression and by the functional state of the alpha 4 beta 7 molecule.
小鼠淋巴细胞向肠道的再循环涉及淋巴细胞整合素α4β7与黏膜血管地址素MAdCAM-1的结合。在人类中，间接证据表明，高表达α4β7的CD4+ T细胞选择性迁移至肠道。我们现在报告，人类成人血液中的CD8+ T细胞和B细胞与CD4+ T细胞一样，α4β7表达具有异质性。相比之下，自然杀伤细胞、嗜酸性粒细胞以及新生儿血液中的T细胞和B细胞α4β7表达相对均一。CD4+和CD8+ T细胞α4β7的表达与年龄、CD45RA表达以及整合素β1（CD29）表达相关，这表明在体内CD4+和CD8+ T细胞初次激活后α4β7表达会发生变化。为了直接确定人类α4β7是否介导与MAdCAM-1的黏附，我们用两种α4β7+人类淋巴瘤细胞系进行了体外黏附试验。结果表明，人类α4β7是MAdCAM-1的受体，而α4β1不是。HUT 78细胞与MAdCAM-1的黏附需要Mn2+，而RPMI 8866细胞的黏附则不需要，这表明α4β7可能至少有两种不同的功能状态。淋巴细胞与MAdCAM-1结合并再循环至黏膜器官的能力可能既受α4β7表达水平的影响，也受α4β7分子功能状态的影响。
