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Therapeutic potential for blockade of the CD40 ligand, gp39

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Conclusions

There is mounting evidence supporting a critical role for gp39-CD40 interactions in the development of both humoral and cellular immune responses. It has been shown that gp39 and CD40 are critical for the development and generation of antibody responses and memory B cells. Evidence for this ligand receptor pair being involved in other types of immune responses is constantly emerging. Experiments in the GVHD system as well as the ability of B cells to tolerize T cells in the presence of anti-gp39 suggest that gp39 and CD40 are also important for the generation of cellular immune responses. The effect on cellular immune responses may be through the control of costimulatory molecules necessary for proper antigen presentation and stimulation. It has been shown that CD40 can control costimulatory molecule expression on several types of antigen-presenting cells; this may be a critical step in the regulation of a cell's ability to present antigen. The role of gp39 and CD40 in the regulation of cytokines, nitric oxide production, and extravasation of cells is just being elucidated but this is potentially yet another tier of immune responses upon which gp39 may have a regulatory effect. Thus, because gp39-CD40 interactions are critical in both the efferent and the afferent arms of the immune response, this ligand-receptor pair is a highly attractive therapeutic target. Blockade of this interaction may lead to enhanced survival of allografts and transplants as well as potentially being able to inhibit a wide spectrum of autoimmune diseases.

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Authors and Affiliations

  1. Graduate Program in Biochemistry, Department of Microbiology, Dartmouth Medical School, 03756, Lebanon, New Hampshire

    Janet E. Buhlmann & Randolph J. Noelle

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  1. Janet E. Buhlmann
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Buhlmann, J.E., Noelle, R.J. Therapeutic potential for blockade of the CD40 ligand, gp39. J Clin Immunol 16, 83–89 (1996). https://doi.org/10.1007/BF01540954

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