VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses
| Autor: | María Mittelbrunn, Ana Ramírez de Molina, Ester Escudero, Francisco Sánchez-Madrid, María M. Escribese, Angeles Ursa, Francisco Mampaso, María Yáñez-Mó, Reyes Tejedor |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Naive T cell Antigen-Presenting Cells Priming (immunology) Integrin alpha4beta1 Lymphocyte Activation Immunological synapse Jurkat Cells Rats Inbred BN Animals Humans Antigen-presenting cell Cells Cultured Multidisciplinary biology Lymphokine VLA-4 Dendritic Cells Dendritic cell Biological Sciences Th1 Cells Flow Cytometry Coculture Techniques Rats Cell biology Microscopy Fluorescence Integrin alpha M biology.protein |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:11058-11063 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0307927101 |
| Popis: | The integrin α4β1 (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 α4β1 during the formation of the immune synapse is currently unknown. Here, we show that α4β1 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-α4 antibodies, VLA-4 colocalizes with the CD3-ζ chain at the center of the synapse. In addition, antibody engagement of α4 integrin promotes polarization toward a T helper 1 (Th1) response in humanin vitromodels of CD4+T cell differentiation and naïve T cell priming by dendritic cells. Thein vivoadministration of anti-α4 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 α4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|