VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses
- 19 July 2004
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 101 (30), 11058-11063
- https://doi.org/10.1073/pnas.0307927101
Abstract
The integrin alpha 4 beta 1 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of alpha 4 beta 1 during the formation of the immune synapse is currently unknown. Here, we show that alpha 4 beta 1 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-alpha 4 antibodies, VLA-4 colocalizes with the CD3-zeta chain at the center of the synapse. In addition, antibody engagement of alpha 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4(+) T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-alpha 4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of alpha 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.Keywords
This publication has 41 references indexed in Scilit:
- JAM2 Interacts with α4β1Published by Elsevier BV ,2002
- Tetraspanins and Intercellular InteractionsMicrocirculation, 2001
- Tetraspanins and Intercellular InteractionsMicrocirculation, 2001
- Fibronectin-Mononuclear Cell Interactions Regulate Type 1 Helper T Cell Cytokine Network in Tolerant Transplant RecipientsThe American Journal of Pathology, 2000
- INDUCTION OF TH1 AND TH2 CD4+T CELL RESPONSES:The Alternative ApproachesAnnual Review of Immunology, 1997
- Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strainsEuropean Journal of Immunology, 1996
- The pathophysiologic role of alpha 4 integrins in vivo.JCI Insight, 1994
- Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cellsEuropean Journal of Immunology, 1991
- Kinetics and pathogenicity of autoantibodies induced by mercuric chloride in the brown Norway ratClinical and Experimental Immunology, 1990
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989