Role of α₄-integrins in lymphocyte homing to mucosal tissues in vivo

Lymphocyte recirculation through different organs is thought to be regulated by adhesion molecules ('homing receptors') recognizing tissue- specific vascular addressins on endothelium. Here we show that the α_{- 4}/β₇-integrin has a key role in the migration of mouse lymphocytes to mucosal sites. Homing to Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments of mAb PS/2 against the α₄-integrin chain, by mAb DAIK32 recognizing a combinatorial epitope on the α₄/β₇-integrin, and by mAb FIB30 against the β₇-chain. The Abs significantly reduce homing of lymphocytes to the intestine, as well. The migration of immunoblasts to gut and gut-associated lymphoid tissue also involves the α₄/β₇-integrin heterodimer. Another anti-α₄ Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab as well as the fibronectin peptide CS-1 are without influence on the migration to Peyer's patches or intestine, in contrast to Ab against the mucosal addressin MAdCAM-1. Thus, homing to gut- associated sites is regulated by the α₄/β₇-integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's patches and intestine by the anti-integrin Abs studied was only partial. L-selectin also participates in the homing of small lymphocytes to mucosal sites, especially Peyer's patches, but does not contribute substantially to the localization of blasts into the intestinal wall. The results support a major, but not exclusive role of the α₄/β₇-integrin in lymphocyte traffic to mucosal sites.