AUTOANTIGEN-SPECIFIC T-CELL PROLIFERATION INDUCED BY THE RIBOSOMAL P2PROTEIN IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

A role for helper T cells in the induction of pathogenic lupus autoant ibodies is increasingly supported by data from studies of murine lupus and patients with systemic lupus erythematosus (SLE). However, the po or in vitro function of SLE T cells has hampered the identification an d characterization of autoantigen-specific T cells. We used recombinan t fusion proteins to study the T cell proliferative response of 31 lup us patients and 27 healthy subjects to a well-characterized SLE autoan tigen, the ribosomal P2 protein. Although PBMC from SLE patients showe d marked impairment in the proliferative response to the common recall antigen tetanus toxoid when compared with normal subjects, a signific antly greater proportion of SLE patients (32%) than normal individuals (0%) showed a T cell response to a recombinant P2 fusion protein. Whe n the SLE patients were subgrouped according to the presence of serum anti-P autoantibody, 7 of 10 anti-P antibody-positive patients, but 0 of 20 anti-P antibody-negative SLE patients, demonstrated > 2,000 cpm [H-3]thymidine incorporation and a P2 stimulation index > 5. The speci ficity of the T cell proliferative response for the P2 protein was con firmed by studies using a second recombinant human P2 fusion protein a nd by the specific activation of P2-primed T cells by recombinant P2 i n secondary cultures. Moreover, the T cell proliferative response to t he P2 autoantigen was mediated by CD4-positive T cells and was inhibit ed by anti-MHC class II antibodies. These data demonstrate the presenc e of autoantigen-specific T helper cells in patients with SLE and sugg est that these T cells drive the production of autoantibodies by B lym phocytes.