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AB0122 Regulatory t cell abnormalities and il-2 deficiency in patients with systemic lupus erythematosus
  1. C. von Spee-Mayer1,2,
  2. N. Wassermann2,
  3. A. Rose1,2,
  4. T. Alexander1,2,
  5. J. Klocke2,
  6. J. Y. Humrich1,2,
  7. G. Riemekasten1,2
  1. 1German Rheumatism Research Center (DRFZ)
  2. 2Rheumatology And Clinical Immunology, CHARITÉ - University Hospital, Berlin, Germany

Abstract

Background Quantitative and qualitative aberrations of CD4+ Foxp3+ regulatory T cells (Treg) have been associated with systemic lupus erythematosus (SLE). In addition, impaired production of IL-2 by T cells has been described in patients with SLE.

Objectives Here, we aim to substantiate the link between IL-2 deficiency and Treg abnormalities in SLE.

Methods Phenotype, frequency and homeostatic proliferation of CD4+Foxp3+CD127lo Treg and CD4+Foxp3- conventional T cell (Tcon) subsets were analyzed by multi-color flow-cytometry in PBMCs from SLE patients and healthy donors ex vivo and after in vitro stimulation with varying doses of human IL-2 (Proleukin). IL-2 mRNA expression of CD4+ T cells in vitro was determined by real-time PCR. Disease activity was determined according to the SLE activity index (SLEDAI).

Results The expression of CD25 in Foxp3+CD127lo Treg was significantly reduced in SLE patients compared to healthy donors. Proliferation of Tcon was significantly increased in SLE patients, resulting in a reduced Treg to Tcon proliferation ratio, which inversely correlated with disease activity. In contrast, the Treg to Tcon proliferation ratio positively correlated with the frequency of CD25+ Treg and with the in vitro IL-2 mRNA expression of CD4+ T cells. Spontaneous in vitro IL-2 mRNA expression of CD4+ T cells was significantly reduced in SLE patients compared to healthy controls.

IL-2 stimulation of SLE PBMCs in vitro significantly augmented CD25 expression levels in Treg. The frequency of CD25high cells among Treg was most efficiently increased when the lowest dose of 1ng/ml IL-2 was applied. In parallel, IL-2 stimulation significantly amplified the expression of anti-apoptotic Bcl-2 in SLE Treg.

Conclusions In analogy to our previous findings in lupus-prone mice (1), Treg from SLE patients show the classical hallmarks of IL-2 deficiency with loss of CD25 expression and a homeostatic imbalance between Treg and Tcon. These findings could be associated with a reduced IL-2 expression by CD4+ T cells in SLE patients. On the other hand, lowdose IL-2 stimulation in vitro could restore these defects, underlying the potential of IL-2 as a novel therapeutic option in SLE.

  1. Humrich, JY et al, PNAS, 2010

Disclosure of Interest None Declared

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