Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Phenotype Characterization of Regulatory T Cells (CD25highCD127low FoxP3) in Systemic Lupus Erythematosus

Mesquita¹, Danilo, Cruvinel², Wilson M., Araujo¹, Julio A. P., Kallas³, Esper G., Andrade¹, Luis Eduardo C.

Universidade Federal de Sao Paulo, Sao Paulo, Brazil,
Universidade Catolica de Goias, Goiania, Brazil,
Universidade de Sao Paulo, Sao Paulo, Brazil

Purpose:

CD4⁺CD25⁺CD127^LOW FoxP3⁺ regulatory T cells (TREG) are specialized in immune response suppression and are apparently involved in the pathogenesis of autoimmune diseases. A variety of TREG surface markers has been described in healthy subjects but not in systemic lupus erythematosus (SLE). This study aimed to characterize the expression of GITR, HLA-DR, PD-1, OX40, CD40L, CD28, CTLA-4 and CD45RO on CD25⁺CD127^LOWFoxP3⁺ TREG cells from patients with active SLE (A-SLE), inactive SLE (I-SLE), and healthy controls (HC).

Method:

Thirty-one patients with A-SLE and 32 patients with I-SLE were sequentially retrieved from the outpatient clinic at the University Hospital. Twenty-six HC were recruited among staff personnel. SLE patients fulfilled the ACR classification criteria. Disease activity was established as SLEDAI equal or above six and disease quiescence was defined as SLEDAI equal to zero. Peripheral blood mononuclear cells (PBMC) were analyzed by multicolor flow cytometry and obtained data were analyzed using the FlowJo software.

Results:

We detected lower frequency of CTLA-4⁺ TREG cells in A-SLE as compared to I-SLE and HC (2.4±4.2, 4.4±6.7, 7.8±10.8, respectively; p<0.05). The same was true for CD28⁺ TREG cells (85.8±12.25, 91±9.7, 92.7±7.9, respectively; p<0.05). In contrast, the frequency of CD40L⁺ TREG cells was higher in A-SLE as compared to I-SLE and HC (5.3±5.4, 2.5±3.1, 0.9±1.2, respectively; p<0.0001). In addition the frequency of CD40L⁺ TREG cells correlated with SLEDAI (r=0.1080, p =0.0163, n=53). The ratio between TREG and effector T cells (Teff) was analyzed for T cell subsets presenting each one of the surface markers. TREG/Teff ratio was decreased in A-SLE and I-SLE as compared to HC for GITR⁺ cells (1.6±1.3, 1.5±0.9, 2.4±1.5, respectively; p<0.05), HLA-DR⁺ cells (1.1±0.6, 1.2±0.5, 1.5±0.6, respectively; p<0.05), OX40⁺ cells (1±0.7, 1±0.6, 1.5±0.9, respectively; p<0.05) and CD45RO⁺ cells (1.1±0.3, 1.2±0.3, 1.4±0.4, respectively; p<0.001). In contrast the TREG/Teff ratio for CD40L+ cells was increased in A-SLE when compared with I-SLE and HC (5±6.3, 2.1±2.1, 1.7±1.8, respectively; p<0.05).

Conclusion:

TREG phenotype evaluation indicated derangements in the cellular and molecular balance of CTLA-4, CD40L, GITR and OX40 on TREG and effector T cells in SLE and highlights potential therapeutic target for this disease.

To cite this abstract, please use the following information:
Mesquita, Danilo, Cruvinel, Wilson M., Araujo, Julio A. P., Kallas, Esper G., Andrade, Luis Eduardo C.; Phenotype Characterization of Regulatory T Cells (CD25highCD127low FoxP3) in Systemic Lupus Erythematosus [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1756
DOI: 10.1002/art.26830

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