Functional CD40 ligand is expressed by T cells in rheumatoid arthritis.
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.
MacDonald
K P
KP
University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia.
Nishioka
Y
Y
Lipsky
P E
PE
Thomas
R
R
D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology; D023201:CD40 Ligand; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012995:Solubility; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D013997:Time Factors; D015854:Up-Regulation
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D023201:CD40 Ligand; D018664:Interleukin-12