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Critical Reviews™ in Immunology
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ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v37.i2-6.100
pages 393-443

Functions of CD40 and Its Ligand, gp39 (CD40L)

Jon D. Laman
Division of Immunological and Infectious Diseases, TNO Prevention and Health (TNO-PG), P. O. Box 2215, 2301 CE Leiden, The Netherlands
Eric Claassen
Division of Immunological and Infectious Diseases, TNO Prevention and Health (TNO-PG), P. O. Box 2215, 2301 CE Leiden, The Netherlands
Randolph J. Noelle
Department of Microbiology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756

RÉSUMÉ

Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is also required for formation of B memory cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells. Defective expression of CD40L in humans leads to an inability to produce isotypes other than IgM (hyper IgM syndrome), and to an absence of germinal centers.
More recent evidence indicates an expansion of the role of the CD40-CD40L axis in cellular interactions beyond antibody formation. Induced expression of CD40 on monocytes can lead to CD40L-activated monocyte effector mechanisms. In addition, CD40-CD40L interactions are crucially involved in development of autoimmune disease in a number of animal models. CD40-CD40L interactions also impact on growth regulation of certain carcinomas. Manipulation of CD40L has also been used to develop novel strategies for long-term antigen-specific tolerization of peripheral T cells. Finally, the CD40-CD40L axis is involved in thymic selection.
Following is a comprehensive overview of CD40L-CD40 interactions in physiological and pathogenic cellular responses and a discussion of the therapeutic ramifications of these interactions.


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