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SAT0160 IL-2 deprivation of FOXP3+ TREG in systemic lupus erythematosus
  1. C. von Spee1,2,
  2. N. Wassermann2,
  3. J.Y. Humrich1,2,
  4. G. Riemekasten1,2
  1. 1German Rheumatism Research Centre (DRFZ)
  2. 2Rheumatology and Clinical Immunology, Charité, Berlin, Germany

Abstract

Background Systemic Lupus Erythematosus (SLE) is characterized by loss of tolerance towards nuclear antigens and uncontrolled activation of self-reactive T and B cells. Several studies have shown phenotypic and quantitative abnormalities of regulatory T cells (Treg) in SLE patients. In addition, impaired IL-2 production by T cells has been connected with SLE. Recently we have demonstrated that an acquired and therapeutically reversible IL-2 deficiency is responsible for the disruption of Treg homeostasis in a lupus mouse model.

Objectives In order to substantiate the rationale for an IL-2-based immunotherapy of human SLE we investigated whether CD4+Foxp3+CD127lo Treg of SLE patients display phenotypic and homeostatic abnormalities that are associated with IL-2 deficiency in analogy to murine lupus.

Methods Phenotype, frequency and proliferative status of CD4+Foxp3+CD127lo Treg and CD4+Foxp3- conventional T cell (Tcon) subsets in peripheral blood from 30 SLE patients and age-matched healthy controls were analyzed by 8-10 colour flow-cytometry. Two-tailed Mann-Whitney U test was used for statistical analysis between the SLE and the control group (p<0.05 is regarded as statistically significant).

Results The overall frequency of Foxp3+CD127lo Treg is significantly increased in SLE patients compared to healthy controls (p=0.003). In contrast, the percentage of CD25 expressing cells among Foxp3+CD127lo Treg is significantly reduced in SLE (p=0.003). The distribution of Treg subsets in SLE patients is shifted towards a memory phenotype with a significantly lower percentage of CD45RA+CCR7+ naive (p=0.001) and higher frequencies of CD45RA-CCR7- effector (p=0.022) and CD45RA-CCR7+ central memory (p=0.025) Treg. The percentage of proliferation, as determined by Ki67 expression, is increased in Treg from SLE patients in contrast to healthy controls (p=0.024). A significantly higher increase in Tcon proliferation however, results in a strongly reduced ratio of Treg proliferation versus Tcon proliferation in SLE patients (P=0.0004). Most proliferating Treg and Tcon belong to the memory/effector subset.

Conclusions Although an increased frequency of Foxp3+CD127lo Treg can be observed in SLE patients, the loss of CD25 expression and the predominance of Treg with a memory/effector phenotype suggest a profound disorder in Treg biology. In parallel, the decreased ratio between proliferating Foxp3+CD127lo Treg and Foxp3- Tcon indicates that the homeostatic balance between Treg and effector T cells is disturbed in SLE patients. Together, Foxp3+CD127lo Treg from SLE patients display phenotypic and homeostatic abnormalities that are very similar to those observed in lupus and IL-2-/- mice, suggesting an IL-2 deprivation of Treg also in human SLE.

Disclosure of Interest None Declared

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