DEFECTIVE B7 EXPRESSION ON ANTIGEN-PRESENTING CELLS UNDERLYING T-CELLACTIVATION ABNORMALITIES IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) PATIENTS

Defective T cell functions, including IL-2 production and proliferatio n, have been shown in SLE patients. After T cell stimulation (first si gnal), a costimulatory signal (second signal) is required to achieve c omplete 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 ex pressed 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 patien ts. We show that stimulation of T cells with phytohaemagglutinin (PHA) in the presence, but not in the absence, of anti-CD28 MoAb or B7(+) c ells results in tyrosine phosphorylation of specific substrates, trans cription of mRNA and production of IL-2 that is indistinguishable in S LE patients and healthy controls. Moreover, proliferation of costimula ted T cells from SLE and controls was specifically abrogated by blocki ng the CD28/B7 interactions by means of addition to the culture of the CTLA4-Ig fusion protein. However, in most patients activated APC fail ed to up-regulate B7 molecules, giving rise to ineffective costimulato ry signalling to T cells. These results indicate that the CD28/B7 cost imulatory pathway is defective in SLE patients.