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Article
Differential Regulation of Soluble and Membrane CD40L Proteins in T Cells
Cellular Immunology
  • Kelli M.G. Matthies, Boise State University
  • Jodie L. Newman, Boise State University
  • Alma Hodzic, Boise State University
  • Denise G. Wingett, Boise State University
Document Type
Article
Publication Date
5-1-2006
DOI
http://dx.doi.org/10.1016/j.cellimm.2006.08.001q
Disciplines
Abstract

CD40 ligand is an important immunoregulatory protein expressed by T cells. This protein exists as two isoforms, a membrane glycoprotein and a truncated soluble form. Here we demonstrate that membrane and soluble CD40L (sCD40L) are differentially regulated depending upon the activation stimulus. In T cell receptor activated cells, both membrane and sCD40L proteins are expressed and CD28 costimulation further increases their expression. The dissection of TCR generated signals into calcium and PKC-dependent pathways demonstrates that calcium is sufficient to induce membrane CD40L yet insufficient for sCD40L. In contrast, sCD40L is preferentially induced by PKC. Moreover, sCD40L production is blocked by Zn2+-dependent metalloproteinase inhibitors while membrane CD40L is concurrently increased. This profile suggests the potential involvement of the ADAM-10 protease which was subsequently shown to cleave membrane CD40L to generate sCD40L. Given the role of sCD40L in numerous disease pathologies and its ability to activate proximal and distal immune responses, the regulated cleavage of CD40L may likely contribute to disease mechanisms.

Citation Information
Kelli M.G. Matthies, Jodie L. Newman, Alma Hodzic and Denise G. Wingett. "Differential Regulation of Soluble and Membrane CD40L Proteins in T Cells" Cellular Immunology (2006)
Available at: http://works.bepress.com/denise_wingett/7/