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Essential Role of OX40L on B Cells in Persistent Alloantibody Production Following Repeated Alloimmunizations

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Abstract

OX40/OX40 ligand (OX40L) interactions are implicated in costimulation for both CD4+ T and B cells in a bidirectional manner. To determine the role of OX40/OX40L interactions in recipient antidonor responses after multiple allogeneic transfusions, we examined alloreactive cytotoxic T lymphocyte (allo-CTL) activity and alloantibody production in repeatedly alloimmunized OX40L-deficient mice. After the fifth alloimmunization, whereas OX40L-deficient mice showed allo-CTL activity with levels comparable to those of wild-type mice, alloantibody production in OX40L-deficient mice was significantly reduced, accompanied by fewer memory B and CD4+ T cells with reduced function. Furthermore, nu/nu mice that received OX40L-deficient T cells still exhibited impaired alloantibody production with fewer memory CD4+ T and B cells. In contrast, RAG-2-deficient mice that received both wild-type T cells and OX40L-deficient B cells produced scant alloantibodies with fewer memory B cells, but sufficient memory CD4+ T cells. Thus, OX40L on B cells, rather than on T cells, is apparently required for adequate and persistent production of alloantibodies after repeated alloimmunizations.

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Authors and Affiliations

  1. Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan

    Hiroshi Kato, Hidefumi Kojima, Yutaka Imai & Testuji Kobata

  2. Department of Oral Surgery, Dokkyo University School of Medicine, Tochigi, Japan

    Hiroshi Kato & Takashi Fujibayashi

  3. Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Naoto Ishii, Hidenori Hase & Kazuo Sugamura

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  1. Hiroshi Kato
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  2. Hidefumi Kojima
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  3. Naoto Ishii
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Correspondence to Hidefumi Kojima.

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Kato, H., Kojima, H., Ishii, N. et al. Essential Role of OX40L on B Cells in Persistent Alloantibody Production Following Repeated Alloimmunizations. J Clin Immunol 24, 237–248 (2004). https://doi.org/10.1023/B:JOCI.0000025445.21894.e5

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