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Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers

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Official URL:http://www.jem.org/cgi/content/abstract/190/8/1115
PubMed:View item in PubMed
Creators Name:Walker, L.S.K. and Gulbranson-Judge, A. and Flynn, S. and Brocker, T. and Raykundalia, C. and Goodall, M. and Foerster, R. and Lipp, M. and Lane, P.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Page Range:1115-1122
Date:18 October 1999
Keywords:CD28, OX40/OX40 Ligand, Germinal Center, Chemokine, T Cell Migration, Animals, Mice
Abstract:Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.
Publisher:Rockefeller University Press (U.S.A.)
Item Type:Article

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