Inverse correlation between CD4+ regulatory T‐cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus

• Published in: Immunology Vol. 117; no. 2; pp. 280 - 286
• Main Authors: Lee, Jyh‐Hong, Wang, Li‐Chieh, Lin, Yu‐Tsan, Yang, Yao‐Hsu, Lin, Dong‐Tsamn, Chiang, Bor‐Luen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2006; Blackwell Science Inc
• Subjects: Adolescent; Antibodies, Antinuclear - blood; Antigens, CD; Antigens, Differentiation - biosynthesis; Antigens, Differentiation - genetics; CD4+ CD25+ regulatory T cells; Child; Child, Preschool; CTLA-4 Antigen; DNA - immunology; Female; Flow Cytometry; Forkhead Transcription Factors - biosynthesis; Forkhead Transcription Factors - genetics; FOXP3; Gene Expression; Glucocorticoid-Induced TNFR-Related Protein; Humans; Immunophenotyping; Lupus Erythematosus, Systemic - immunology; Male; Original; Polymerase Chain Reaction - methods; real‐time PCR; Receptors, Interleukin-2 - analysis; Receptors, Nerve Growth Factor - biosynthesis; Receptors, Nerve Growth Factor - genetics; Receptors, Tumor Necrosis Factor - biosynthesis; Receptors, Tumor Necrosis Factor - genetics; RNA, Messenger - genetics; Severity of Illness Index; systemic lupus erythematosus; T-Lymphocytes, Regulatory - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2005.02306.x

Summary CD4+ CD25+ regulatory T cells (Tregs) are critical in maintaining self‐tolerance and preventing organ‐specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real‐time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA‐4, and GITR, we characterized CD4+ CD25+ T cells in paediatric SLE patients and healthy subjects. The frequency of CD4+ CD25+ Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7·27% ± 2·50%, 9·59% ± 2·80% and 9·78% ± 2·11%, respectively; P = 0·027 and P < 0·001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores (r = −0·59, P = 0·001) and serum anti‐double‐stranded DNA levels (r = −0·65, P < 0·001). Our preliminary investigations found elevated surface expression of GITR in CD4+ CD25+ T cells, elevated mRNA expression of CTLA‐4 in CD4+ T cells and higher amounts of mRNA expression for FOXP3 in CD4+ cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4+ CD25+ Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA‐4 and GITR imply the possible role of CD4+ Tregs in the pathogenesis of SLE.