Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.

Original publication

DOI

10.1084/jem.189.7.1025

Type

Journal article

Journal

Journal of Experimental Medicine

Publisher

Rockefeller University Press

Publication Date

05/04/1999

Volume

189

Pages

1025 - 1031