Defective antigen-presenting cell function in patients with systemic lupus erythematosus

Abstract

Objective: Patients with systemic lupus erythematosus (SLE) who exhibit defective in vitro responses to recall antigens and normal responses to alloantigens have been shown to have an abnormality in antigen-presenting cell (APC) function. This study was undertaken to further characterize this defect in APC function in lupus patients.

Methods: Mononuclear cells (MNC) from the peripheral blood of patients with SLE and from normal individuals were cultured in the presence of either recall antigen tetanus toxoid (TT), anti-CD3 (OKT3) monoclonal antibody, or alloantigens, and proliferative or interleukin-2 responses were assessed. Cell surface expression of B7-1 was assessed by flow cytometry.

Results: MNC from all normal individuals and from 7 patients with SLE responded to both TT and alloantigen and were designated +/+. Twelve SLE patients did not respond to TT but did respond to alloantigen stimulation and were designated -/+. In both normal subjects and SLE patients, the ability to respond to OKT3 correlated strongly with the ability to respond to recall antigen. A defect in APC costimulatory function was suggested by data demonstrating that interferon-gamma-induced expression of B7-1 was significantly reduced in SLE patients compared with controls. Neither controls nor SLE patients expressed detectable amounts of surface B7-1 molecule on resting APC. Defective recall and anti-CD3-stimulated responses could be enhanced in SLE patients in the presence of B7/BBl-transfected P815 murine mastocytoma cells underscoring an SLE-associated defect in costimulatory activity. However, nontransfected P815 cells were also able to enhance responses to OKT3 in -/+ patients; blocking experiments showed that this was mediated through an IgG Fc receptor-dependent mechanism.

Conclusion: These data indicate that SLE-associated defects in APC function in vitro can be accounted for by abnormalities in APC surface membrane molecules such as B7, IgG Fc receptors, and possibly others.