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)