The Journal of Experimental Medicine
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Published 5 April 2004. doi:10.1084/jem.20031705
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 7, 1025-1031
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Brief Definitive Report

The Modulation of CD40 Ligand Signaling by Transmembrane CD28 Splice Variant in Human T Cells

Sebastian A. Mikolajczaka,b, Bruce Y. Maa,b, Tetsuya Yoshidaa,b, Ryoko Yoshidaa,b, David J. Kelvina,b, and Atsuo Ochia,b

a University Health Network, Toronto, Ontario M5G 2C4, Canada
b Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario N6G 2V4, Canada

Address correspondence to Atsuo Ochi, University Health Network, 200 Elizabeth St., MBRC-SR425, Toronto, Ontario M5G 2C4, Canada. Phone: (416) 340-4800; Fax: (416) 340-4596; email: aochi{at}uhnresearch.ca

The role of CD40 ligand (CD40L)/CD40 signaling in T cell–dependent B cell differentiation and maturation has been amply documented. The mechanism of CD40 signaling in B cells has been well established, whereas the signaling mechanism of CD40L in T cell costimulation remains unknown. In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells. The cross-linking of CD40L resulted in the coendocytosis of CD28i with CD40L. The tyrosine phosphorylation of CD28i followed the cross-linking of CD40L, and the overexpression of CD28i augmented the c-Jun NH2-terminal kinase, p21-activated kinase 2, and nuclear factor {kappa}B activation. These data indicate that CD28i, by functioning as a signaling adaptor, transduces CD40L signaling as well as CD28 signaling in human T cells.

Key Words: CD40L • CD28 • CD28 variant • T cell costimulation


S.A. Mikolajczak and B.Y. Ma equally contributed to this work.

B.Y. Ma's present address is Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.

T. Yoshida's and R. Yoshida's present address is First Department of Internal Medicine, School of Medicine, Fukuoka University, Nanakuma 7-45-1, Jonan-Ku, Fukuoka 814-0180, Japan.


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