Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients

Clin Exp Immunol. 1996 Apr;104(1):72-9. doi: 10.1046/j.1365-2249.1996.d01-648.x.

Abstract

Defective T cell functions, including IL-2 production and proliferation, have been shown in SLE patients. After T cell stimulation (first signal), a costimulatory signal (second signal) is required to achieve complete T cell activation. Main costimulatory signals are provided to T cells by B7 antigens (CD80 and CD86, expressed on antigen-presenting cells (APC)) upon interaction with its receptor, the CD28 molecule expressed on T cells. The aim of this study was to investigate the role of CD28/B7 interactions in the impaired T cell responses of SLE patients. We show that stimulation of T cells with phytohaemagglutinin (PHA) in the presence, but not in the absence, of anti-CD28 MoAb or B7+ cells results in tyrosine phosphorylation of specific substrates, transcription of mRNA and production of IL-2 that is indistinguishable in SLE patients and healthy controls. Moreover, proliferation of costimulated T cells from SLE and controls was specifically abrogated by blocking the CD28/B7 interactions by means of addition to the culture of the CTLA4-Ig fusion protein. However, in most patients activated APC failed to up-regulate B7 molecules, giving rise to ineffective costimulatory signalling to T cells. These results indicate that the CD28/B7 costimulatory pathway is defective in SLE patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adult
  • Antigen-Presenting Cells / immunology
  • Antigens, CD
  • Antigens, Differentiation / physiology
  • B7-1 Antigen / immunology*
  • CD28 Antigens / physiology*
  • CTLA-4 Antigen
  • Female
  • Gene Expression
  • Humans
  • Immunoconjugates*
  • Interleukin-2 / genetics
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation
  • RNA, Messenger / genetics
  • Signal Transduction
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Interleukin-2
  • RNA, Messenger
  • Abatacept