Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice

Using lymphocyte function-associated. antigen (LFA)-1(-/-) mice, we have ex amined the role of LFA-1 and other integrins in the recirculation of lympho cytes. LFA-1 has a key role in migration to peripheral lymph nodes (pLNs), and influences migration into other LNs. Second, the alpha 4 integrins, alp ha 4 beta 7 and alpha 4 beta 1, have a hitherto unrecognized ability to com pensate for the lack of LFA-1 in migration to pLNs. These findings are conf irmed using normal mice and blocking LFA-1 and a4 monoclonal antibodies. Un expectedly, vascular cell adhesion molecule (VCAM)-1, which is essential in inflammatory responses, serves as the ligand for the alpha 4 integrins on pLN high endothelial venules. VCAM-1 also participates in trafficking into mesenteric LNs and Peyer's patch nodes where mucosal addressin cell adhesio n molecule 1 (MAdCAM-1), the alpha 4 beta 7-specific ligand, dominates. Bot h alpha 4 beta 1, interacting with ligand VCAM-1, and also LFA-1 participat e in substantial lymphocyte recirculation through bone marrow. These observ ations suggest that organ-specific adhesion receptor usage in mature lympho cyte recirculation is not as rigidly adhered to as previously considered, a nd that the same basic sets of adhesion receptors are used in both lymphocy te homing and inflammatory responses.