Histone-specific Th0 and Th1 clones derived from systematic lupus erythematosus patients induce double-stranded DNA antibody production

Abstract

Objective. To investigate whether histone-specific T helper (Th) cells that are able to induce anti-double-stranded DNA (anti-dsDNA) antibodies can be isolated from patients with systemic lupus erythematosus (SLE) and to characterize the cytokine secretion pattern of such Th clones. Methods. Peripheral mononuclear cells from SLE patients and healthy donors were stimulated with autologous apoptotic cell material or purified histones, expanded with interleukin-2 (IL-2), and cloned by limiting dilution. Histone reactivity of clones was examined by histone-specific proliferation and cytokine release. Cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and CTLL-2 bioassay. Induction of anti-dsDNA antibodies was measured in cocultures of autologous B cells and Th clones by ELISA. Results. Numerous histone-specific T cell receptor (TCR) α/β+ Th clones were established from 2 of 3 patients with active SLE and from 1 of 2 healthy individuals. Most Th clones secreted IL-2, interferon-γ (IFNγ), and IL-4, whereas some produced predominantly IL-2 and IFNγ. Th clones that could stimulate the production of anti-dsDNA antibodies were derived from SLE patients and from a healthy individual. Conclusion. Th cells specific for histones may play an important role in the pathogenesis of SLE by inducing autoantibodies to dsDNA. Both Th1 and Th2 cytokines may be involved in the pathogenesis of SLE. The presence of histone-specific Th cells in a healthy individual indicates the importance of peripheral tolerance for preventing autoimmunity to nuclear antigens.