Expression of VLA-4 and L-selectin in human gut-associated lymphoid tissue (GALT).

Abstract

The preferential homing of lymphocytes to certain tissue sites has been studied in several species19,12. Peyer’s patches (PP) and the appendix have been considered primarily as B-cell structures. However, a recent study of lymphocyte homing in rats revealed no special prefence for thoracic duct-derived B or T cells to bind to PP high endothelial venules (HEVs)22. In mice, two heterodimeric integrins are assumed to mediate lymphocyte homing to PP: LPAM-1 consisting of α4 coupled to a β chain designated βp, and LPAM-2 (α4βl), which is homologous to the human very late antigen-4 (VLA-4)7,8. However, in humans α4 may also be coupled to β7, homologous to mouse βp14,9,16. The endothelial counter-receptor (ligand) for α4β1, vascular adhesion molecule-1 (VCAM-1), is expressed in two isoforms with 6 or 7 immunoglobulin-like domains (6D and 7D): VCAM-7D is the dominant form found on endothelium of inflamed tissues while VCAM-6D (defined by monoclonal antibody (mAb) El/6) apparently is expressed earlier during inflammation but scarcely on human GALT HEVs21,13,15. The ligand for α4β7 is as yet unknown, although stimulated lymphocytes expressing this heterodimer can bind to VCAM-13. However, the efficiency of binding to VCAM-1 was much better for lymphocytes expressing α4β1 than α4β73. A mAb to β7 inhibited lymphocyte binding to PP but not peripheral lymph node (PLN) HEVs in mice9, suggesting that β7 might be responsible for PP-specific lymphocyte migration in the normal state.