Functional CD40 ligand is expressed by T cells in rheumatoid arthritis

J Clin Invest. 1997 Nov 1;100(9):2404-14. doi: 10.1172/JCI119781.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • B-Lymphocytes / physiology
  • CD40 Ligand
  • Cell Membrane / metabolism
  • Dendritic Cells / immunology
  • Gene Expression
  • Humans
  • Interleukin-12 / metabolism
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism*
  • RNA, Messenger / genetics
  • Solubility
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / ultrastructure
  • Time Factors
  • Up-Regulation


  • Membrane Glycoproteins
  • RNA, Messenger
  • CD40 Ligand
  • Interleukin-12