Integrins and L-selectin in lymphocyte-endothelium interactions and homing into gut-associated tissue

Abstract

The selective entry of subpopulations and distinct differentiation stages of lymphocytes into different tissues is thought to be mediated by interaction of endothelial ligands with adhesion molecules on lymphocytes. L-selectin has been considered as a peripheral lymph node-specific homing receptor and alpha 4-integrins have been supposed to mediate entry into mucosa-associated lymphoid tissue. In vivo homing studies show that the specificity is not so clear-cut. The MEL-14 antibody indeed blocks almost completely lymphocyte homing into peripheral lymph nodes. However, entry into Peyer's patches and even the intestine itself is also affected. Thus, L-selectin plays a broader part as previously thought. Some antibodies against the alpha 4 and beta 1-integrin chain inhibit selectively lymphocyte homing to Peyer's patches by 50-70%. alpha 4-integrins therefore seem to be important for homing into mucosa-associated tissue, although a considerable fraction of cells does not require this molecule (or this epitope) for recognition of Peyer's patch endothelium. In vitro and in vivo data indicate that neither VCAM-1 nor fibronectin play a role for homing into Peyer's patches; most likely a further ligand recognized by distinct epitopes of alpha 4 is used for recognition of Peyer's patch HEV. A combination of the mAbs MEL-14 and PS/2.3 blocks nearly completely the localization in Peyer's patches. Beside alpha 4-integrins, the beta 2-integrin LFA-1 has been shown to be involved in lymphocyte recirculation. Also combinations of antibodies against LFA-1 and L-selectin as well as of anti LFA-1 with anti alpha 4 show synergistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)