The cytokine memory of SmD1^83-119-autoantigen-specific Th cells of systemic lupus erythematosus patients

Objective

The aim of the study was to analyze the cytokine memory of Th cells derived from systemic lupus erythematosus (SLE) patients and healthy donors enriched for autoantigen-specific T cells by in vitro stimulation with SmD1^83-119, a common autoantigen in SLE.

Method

Autoreactive CD3⁺ T cells derived from 37 SLE patients and 14 healthy donors were enriched by repetitive ex vivo stimulation of peripheral blood mononuclear cells with SmD1^83-119. For control, peripheral blood mononuclear cells were stimulated only with IL-2. After two rounds of antigen stimulations, cultures were stimulated with phorbol 12-myristate 13-acetate/ionomycin for intracellular cytokine staining. Frequencies of cytokine-expressing T cells were analyzed and, in SLE patients, compared with disease activities and autoantibody levels.

Results

Comparing cultures from SLE patients with those from healthy donors, SLE patients displayed higher frequencies of tumor necrosis factor alpha-positive T cells and the frequencies correlated with disease activity. SmD1^83-119-induced tumor necrosis factor alpha expression correlated with serum anti-dsDNA antibody levels. The frequencies of IL-10-expressing T cells were lower in cultures from SLE patients. Cultures from patients with high frequencies of IL-10⁺ T cells revealed low disease activities. SmD1^83-119-induced increases in IL-10-expressing T cells were associated with low anti-dsDNA and anti-SmD1^83-119 antibody levels in culture supernatants.

Conclusion

The enrichment of SmD1^83-119-reactive T cells by in vitro cultures showed that cytokine changes specifically occur in lupus patients. The results give insight into the cytokine memory of autoreactive Th cells and their role in lupus pathogenesis.