DECREASED T-CELL RESPONSE TO ANTI-CD2 IN SYSTEMIC LUPUS-ERYTHEMATOSUSAND REVERSAL BY ANTI-CD28

Objective. To assess the ability of T cells from patients with systemi c lupus erythematosus (SLE) to respond to a mitogenic combination of a nti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect. Methods. Peripheral blood mononuclear cell ( PBMC) populations from individuals with SLE and paired controls were s timulated in vitro with anti-CD2, and the proliferative response was c ompared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb. Results. The proli ferative response to anti-CD2 was decreased to a greater extent than w as the response to anti-CD3 or PHA in SLE patients, This defect was fo und in approximately one-half of the patients examined, was not associ ated with disease activity, and was maintained upon repeated testing, Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-third s of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from no rmal donors corrected the defect. The addition to PBMC of anti-CD28, b ut not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect, Significantly fewer CD8+ T cells ex pressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells. Conclusion. This study provides evidence that s ome functional T cell defects in SLE mag be due, at least in part, to decreased CD28-mediated costimulatory activity following the interacti on of T cells with conventional accessory cells.