HISTONE-SPECIFIC THO AND TH1 CLONES DERIVED FROM SYSTEMIC LUPUS-ERYTHEMATOSUS PATIENTS INDUCE DOUBLE-STRANDED DNA ANTIBODY-PRODUCTION

Objective. To investigate whether histone-specific T helper (Th) cells that are able to induce anti-double-stranded DNA (anti-dsDNA) antibod ies can be isolated from patients with systemic lupus erythematosus (S LE) and to characterize the cytokine secretion pattern of such Th clon es. Methods. Peripheral blood 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 his tone-specific proliferation and cytokine release, Cytokines were deter mined by enzyme-linked immunosorbent assay (ELISA) and CTLL-2 bioassay , Induction of anti-dsDNA antibodies was measured in cocultures of aut ologous B cells and Th clones by ELISA. Results. Numerous histone-spec ific T cell receptor (TCR) alpha/beta+ 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-gamma (IFN gamma), and IL-4, whereas some produced predominantly IL-2 and IFN gamma, 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 o f SLE by inducing autoantibodies to dsDNA. Both Th1 and Th2 cytokines may be involved in the pathogenesis of SLE, The presence of histone-sp ecific Th cells in a healthy individual indicates the importance of pe ripheral tolerance for preventing autoimmunity to nuclear antigens.