Open AccessDefective B7 expression on antigen‐presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients
Author(s) -
GARCÍACÓZAR F. J.,
MOLINA I. J.,
CUADRADO M. J.,
MARUBAYASHI M.,
PEÑA J.,
SANTAMARÍA M.
Publication year - 1996
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1996.d01-648.x
Subject(s) - cd80 , cd28 , cd86 , immunology , t cell , biology , clonal anergy , antigen presenting cell , antigen , co stimulation , zap70 , immune system , t cell receptor , microbiology and biotechnology , cytotoxic t cell , cd40 , biochemistry , in vitro
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.