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© The Rockefeller University Press, 0022-1007/2000/1/365/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 2, January 17, 2000 365-374


Original Article

Impairment of Antigen-Presenting Cell Function in Mice Lacking Expression of Ox40 Ligand

Kazuko Murataa,b, Naoto Ishiia, Hiroshi Takanod, Shigeto Miuraa,b, Lishomwa C. Ndhlovua, Masato Nosec, Tetsuo Nodab,d, and Kazuo Sugamuraa,b

a Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan
b Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan
c Second Department of Pathology, Ehime University School of Medicine, Ehime 791-02, Japan
d Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170, Japan
Department of Microbiology and Immunology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.81-22-717-809781-22-717-8096

sugamura{at}mail.cc.tohoku.ac.jp

OX40 expressed on activated T cells is known to be an important costimulatory molecule on T cell activation in vitro. However, the in vivo functional significance of the interaction between OX40 and its ligand, OX40L, is still unclear. To investigate the role of OX40L during in vivo immune responses, we generated OX40L-deficient mice and a blocking anti-OX40L monoclonal antibody, MGP34. OX40L expression was demonstrated on splenic B cells after CD40 and anti-immunoglobulin (Ig)M stimulation, while only CD40 ligation was capable of inducing OX40L on dendritic cells. OX40L-deficient and MGP34-treated mice engendered apparent suppression of the recall reaction of T cells primed with both protein antigens and alloantigens and a significant reduction in keyhole limpet hemocyanin–specific IgG production. The impaired T cell priming was also accompanied by a concomitant reduction of both T helper type 1 (Th1) and Th2 cytokines. Furthermore, antigen-presenting cells (APCs) derived from the mutant mice revealed an impaired intrinsic APC function, demonstrating the importance of OX40L in both the priming and effector phases of T cell activation. Collectively, these results provide convincing evidence that OX40L, expressed on APCs, plays a critical role in antigen-specific T cell responses in vivo.

Key Words: OX40 ligand • antigen-presenting cell function • T cell priming • OX40 ligand mutant mice • cytokine


Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; ES, embryonic stem; HEL, hen egg lysozyme; s, soluble.

© 2000 The Rockefeller University Press


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