The systemic and SmD183–119–autoantigen-specific cytokine memory of Th cells in SLE patients

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Abstract

Objectives

The aim of the study was to analyse the cytokine memory of T-cells derived from systemic lupus erythematosus (SLE) patients and healthy donors enriched for autoantigen-specific T-cells by in vitro stimulation with SmD183–119, a common autoantigen in SLE.

Methods

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 (PBMCs) with SmD183–119. For control, PBMCs were stimulated only with interleukin-2 (IL-2). After two rounds of antigenic stimulation, cultures were stimulated with PMA/ionomycin to probe the cytokine memory by intracellular cytokine staining. Frequencies of cytokine-expressing T-cells were analysed and, in SLE patients, compared with disease activities and autoantibody levels.

Results

Comparing the cytokine memory in the cultures, SLE patients displayed higher frequencies of tumour necrosis factor-α (TNF-α)+ T-cells than healthy donors and the frequencies correlated with disease activity. Frequencies of SmD183–119-specific TNF-α+ T-cells and of memory T-cells expressing interferon-γ (IFN-γ) correlated with serum anti-dsDNA antibody levels. The frequencies of IL-10 expressing SmD183–119-specific T-cells were lower among PBMCs of SLE patients. Relatively higher frequencies of IL-10+ T-cells in SLE patients correlated with low disease activities, and low anti-dsDNA and anti-SmD183–119 antibody concentrations in culture supernatants.

Conclusions

The memory of autoreactive SmD183–119-specific and unspecific stimulated peripheral Th cells for re-expression of cytokines is shifted towards more cells expressing TNF-α and less IL-10+ cells, when compared SLE patients with normal donors. This shift towards proinflammatory memory effector Th cells correlates with disease severity and humoral autoimmunity.

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