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 species^19,12. 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 βp^14,9,16. 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 HEVs^21,13,15. 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.