Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis

• Published in: Clinical and experimental immunology Vol. 153; no. 1; pp. 44 - 55
• Main Authors: Yates, J, Whittington, A, Mitchell, P, Lechler, R.I, Lightstone, L, Lombardi, G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2008; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Adolescent; Adult; Analysis of Variance; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Case-Control Studies; CD4+ CD25+ regulatory T cell; CD4⁺ CD25⁺ regulatory T cell; Child; Child, Preschool; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Interleukin-2 Receptor alpha Subunit - immunology; Kidneys; Lupus Nephritis - immunology; Lymphocyte Count; Male; Medical sciences; Middle Aged; Molecular biophysics; Nephrology. Urinary tract diseases; nucleosomes; Nucleosomes - immunology; SLE; Statistics, Nonparametric; T-Lymphocytes, Regulatory - immunology; Translational Studies; Urinary system involvement in other diseases. Miscellaneous; Kidney disease; Human; Immunopathology; Connective tissue disease; Skin disease; Urinary system disease; Cell function; Autoimmune disease; Biochemistry; Lupus nephritis; SLE; nucleosomes; Systemic disease; T-Lymphocyte; Molecular biology; CD4+ CD25+ regulatory T cell
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2008.03665.x

CD4⁺ CD25⁺ regulatory T cells have been shown to be a vital component of the mechanisms that prevent autoreactivity in mice and also in humans. Previous studies have examined CD4⁺ CD25hi regulatory T cell frequency and function in patients with systemic lupus erythematosus (SLE) with mixed results. We investigated frequency, phenotype and function in 21 patients with SLE and six with inactive disease. We found no reduction in frequency of the CD25hi subset, although active disease was associated with an increased proportion of CD4⁺ CD25⁺ T cells. When examining function, in the majority of individuals suppression was comparable with controls, although cells isolated from one patient with active disease failed to suppress proliferation. On testing the effect of CD25hi depletion on the responses of whole peripheral blood mononuclear cells to nucleosomes we found that, where a response was detectable from patients, depletion augmented interferon-γ secretion, demonstrating intact suppression of responses implicated in the pathogenesis of SLE. Our results did not confirm an association of failure in CD4⁺ CD25hi regulatory T cell function or a reduction in their frequency with active disease. Instead, perturbations in the CD4⁺ CD25hi regulatory T cell population may play a role in disease in only a minority of the patients afflicted by the diverse syndromes of SLE.