A role for helper T cells in the induction of pathogenic lupus
autoantibodies is increasingly supported by data from studies of murine lupus and patients with
systemic lupus erythematosus (SLE). However, the poor in vitro function of SLE T cells has hampered the identification and characterization of
autoantigen-specific T cells. We used
recombinant fusion proteins to study the T cell proliferative response of 31 lupus patients and 27 healthy subjects to a well-characterized SLE
autoantigen, the
ribosomal P2 protein. Although PBMC from SLE patients showed marked impairment in the proliferative response to the common recall
antigen tetanus toxoid when compared with normal subjects, a significantly greater proportion of SLE patients (32%) than normal individuals (0%) showed a T cell response to a recombinant P2 fusion
protein. When 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 [3H]
thymidine incorporation and a P2 stimulation index > 5. The specificity of the T cell proliferative response for the P2
protein was confirmed by studies using a second recombinant human P2 fusion
protein and by the specific activation of P2-primed T cells by recombinant P2 in secondary cultures. Moreover, the T cell proliferative response to the P2
autoantigen was mediated by CD4-positive T cells and was inhibited by anti-MHC class II
antibodies. These data demonstrate the presence of
autoantigen-specific T helper cells in patients with SLE and suggest that these T cells drive the production of
autoantibodies by B lymphocytes.