Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand

Kazuko Murata, Naoto Ishii, Hiroshi Takano, Shigeto Miura, Lishomwa C. Ndhlovu, Masato Nose, Tetsuo Noda, Kazuo Sugamura

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257 Citations (Scopus)


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 printing 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.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalJournal of Experimental Medicine
Issue number2
Publication statusPublished - 2000 Jan 17


  • Antigen-presenting cell function
  • Cytokine
  • OX40 ligand
  • OX40 ligand mutant mice
  • T cell priming


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