Cross-talk between CD40 and CD40L: lessons from primary immune deficiencies.
OBJECTIVE
The purpose of this review is to provide an update of the molecular bases of CD40-mediated signalling and of the human immune defects associated with abnormalities of this activation pathway.


RESULTS
Over the last years considerable progress in the identification of intracellular molecules mediating CD40 signalling has been achieved. This review focuses on the recent work on the molecular mechanisms of CD40 signalling mediated by tumor necrosis factor receptor-associated factors, by transcription of the activation-induced cytidine deaminase gene and by activation of nuclear factor kappa B. Furthermore, the importance of CD40/CD40L interaction for the induction of adaptive immunity will be outlined in the context of primary immunodeficiencies due to defects of the genes involved in the CD40 signalling pathway, which are characterized by an immunological phenotype of hyper-IgM syndrome.


CONCLUSIONS
The critical role of CD40/CD40L interactions in the development of various disease states has been fully appreciated, and further understanding of the molecular events involved in CD40 signalling may allow the identifications of candidate genes for other hyper-IgM syndromes. Molecular diagnosis will help to provide the most appropriate treatment and prognosis.
Ferrari
Simona
S
Institute of Molecular Medicine Angelo Nocivelli, Pediatrics Clinic, University of Brescia, Brescia, Italy.
Plebani
Alessandro
A
D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007107:Immune System / Q000502:physiology; D016867:Immunocompromised Host / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology* / Q000503:physiopathology; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D019013:CD40 Antigens; D023201:CD40 Ligand