CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather than suppress, spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis

Abstract

The cellular requirements for B cell hyperactivity in systemic lupus erythematosus (SLE) were studied. Removal of either CD8+ or CD4+ lymphocyte markedly decreased the spontaneous in vitro production of polyclonal IgG and of antigen-specific (anti-double-stranded DNA and antinucleoprotein) antibodies by SLE peripheral blood mononuclear cells (PBMC). The CD8+ lymphocytes that sustained IgG production were CD3+, HLA-DR+, and their activity was abrogated by preincubation with anti-HLA-DR monoclonal antibody. When both CD4+ and CD8+ cells were removed, the readdition of either subset partially restored polyclonal IgG production, but both cell subsets were required to reconstitute autoantibody production. Purified SLE B cell cultures, which generated only 15% of the IgG produced by unseparated PBMC, were fully reconstituted only by mixtures of CD4+ with CD8+ cells, and with CD8-, CD4-, CD16+ cells. At least part of the support for spontaneous IgG production can be attributed to endogenous interleukin-2 and interleukin-6.