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  • 标题:VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses
  • 本地全文:下载
  • 作者:María Mittelbrunn ; Ana Molina ; María M. Escribese
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2004
  • 卷号:101
  • 期号:30
  • 页码:11058-11063
  • DOI:10.1073/pnas.0307927101
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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 naive 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.
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