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OP0220 Pathogenic Role of IL-10 Producing Helper T Cells in Systemic Lupus Erythematosus
  1. F. Facciotti1,
  2. A.E. Penatti2,
  3. S. Zeni3,
  4. S. Abrignani1,
  5. P. Meroni2,
  6. J. Geginat1
  1. 1Autoimmunity Unit, INGM, National Institute of Molecular Genetic
  2. 2Dept. Clin. Sciences & Comm. Health, University of Milan, G. Pini Institute, Rheumatology Dept
  3. 3Rheumatology Dept., G. Pini Institute, Milano, Italy

Abstract

Background IL-10 is a potent anti-inflammatory cytokine that contributes to the suppressive functions of regulatory T-cells, but it is also a well-known B cell growth and differentiation factor produced by CD4+ helper T-cells. Consequently, IL-10 is pathogenic in systemic lupus erythematosus (SLE) where it promotes autoantibody production and nephritis. We have previously shown that human CCR6+ memory T cells produce IL-10 in secondary lymphoid organs, and more recently we found that they promote B cell antibody production via IL-10, but are distinct from follicular helper (TFH) and Th17 cells.

Objectives To monitor the frequency and function of IL-10-producing B helper T cells in SLE patients and to evaluate their association with disease activity.

Methods Blood samples from 40 clinically well-characterized SLE patients and 25 healthy donors (HD) were included. Composition of different T cell subsets in peripheral blood according to surface markers expression and intracellular cytokine production were assessed by flow cytometry. The frequencies of T cell subsets were correlated with disease activity (measured by the SELENA-SLEDAI index). To assess B helper functions, T cell subsets and B cells from SLE patients and HD were co-cultured ex vivo and IgG production was measured in supernatants by ELISA.

Results IL10-producing CCR6+ memory T cells, but not TFH cells were significantly expanded in the peripheral blood of SLE patients as compared to HD. Importantly, the frequency of CCR6+ memory T cells and serum levels of IL-10, but not of IL-17, correlated with disease activity. Ex vivo sorted CCR6+ helper T cells from blood of SLE patients produced high levels of IL-10 upon co-culture with B cells and promoted IgG production. Strikingly, CD25+ Tregs suppressed B cell help provided by CCR6+ T cells in HD, but not in SLE patients.

Conclusions Our results demonstrated that accumulation of IL-10-producing CCR6+CD4+ memory T cells correlates with SLE disease activity, supporting a pathogenic role of these helper T cells.This hypothesis is corroborated by functional experiments, which demonstrate a Treg-resistant B helper capacity of IL-10-producing CCR6+ T cells in SLE patients. Therefore, CCR6+IL10-producing helper T cells represent a potential therapeutic target and/or diagnostic/prognostic marker of disease activity in SLE patients.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5485

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