Selective antibody blockade of lymphocyte migration to mucosal sites and mast cell adhesion

The integrins α₄β₇ and α₄β₁ mediate adhesion to the mucosal addressin cell adhesion molecule-1 (MAdCAM-I) and the vascular cell adhesion molecule-1 (VCAM-1) and are important in T cell and allergic inflammatory reactions in the rat. The relative contributions of α₄β₇ and α₄β₁ in these reactions is unknown. To examine the role of α₄β₇ in the rat a new mAb, TA-6, was developed. TA-6 inhibited adhesion to MAdCAM-1 but not to VCAM-1, a characteristic of α₄β₇ adhesion, and immunofluorescence and immunoprecipitation studies were compatible with binding to α₄β₇. TA-6 blocked rat lymphocyte adhesion to mesenteric lymph nodes and T cell migration to mucosal lymphoid tissues and it bound to rat mucosal mast cells. TA-6 did not inhibit lymphocyte adhesion to peripheral lymph nodes and T cell migration to peripheral lymphoid tissues or cutaneous inflammatory sites, and was not expressed on connective tissue mast cells.