Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells

Academic Article

Abstract

  • Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (RelA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of IL-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of IκBα following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel- containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Bryan RG; Li Y; Lai JH; Van M; Rice NR; Rich RR; Tan TH
  • Start Page

  • 7933
  • End Page

  • 7942
  • Volume

  • 14
  • Issue

  • 12