Work

Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.

Year: 1997

Type: article

Abstract: CD40 ligand (CD40-L), a member of the tumor necrosis family of transmembrane glycoproteins, is rapidly and transiently expressed on the surface of recently activated CD4+ T cells. Interactions between CD40-L and CD40 induce B cell immunoglobulin production as well as monocyte activation and dendritic cell differentiation. Since these features characterize rheumatoid arthritis (RA), the expression and function of CD40-L in RA was examined. Freshly isolated RA peripheral blood (PB) and synovial fluid (SF) T cells expressed CD40-L mRNA as well as low level cell surface CD40-L. An additional subset of CD4+ RA SF T cells upregulated cell surface CD40-L expression within 15 min of in vitro activation even in the presence of cycloheximide, but soluble CD40-L was not found in SF. CD40-L expressed by RA T cells was functional, since RA PB and SF T cells but not normal PB T cells stimulated CD40-L-dependent B cell immunoglobulin production and dendritic cell IL-12 expression in the absence of prolonged in vitro T cell activation. In view of the diverse proinflammatory effects of CD40-L, this molecule is likely to play a central role in the perpetuation of rheumatoid synovitis. Of importance, blockade of CD40-L may prove highly effective as a disease modifying therapy for RA.

Source: Journal of Clinical Investigation

DOI: 10.1172/jci119781

Authors: K P MacDonald, Y Nishioka, P E Lipsky, R Thomas

Institutions: The University of Queensland, Princess Alexandra Hospital, The University of Texas Southwestern Medical Center

Language: English

Topic: Rheumatoid Arthritis Research and Therapies

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Arthritis Foundation, Arthritis Foundation of Australia, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases