Prolonged expression of CD154 on CD4 T cells from pediatric lupus patients correlates with increased CD154 transcription, increased nuclear factor of activated T cell activity, and glomerulonephritis
Open Access
- 3 August 2010
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 62 (8), 2499-2509
- https://doi.org/10.1002/art.27554
Abstract
Objective To assess CD154 expression in patients with pediatric systemic lupus erythematosus (SLE) and to explore a transcriptional mechanism that may explain dysregulated expression of CD154. Methods Cell surface CD154 expression (pre‐ and postactivation) in peripheral blood CD4 T cells from 29 children with lupus and 29 controls matched for age, sex, and ethnicity was examined by flow cytometry. CD154 expression was correlated with clinical features, laboratory parameters, and treatments received. Increased CD154 expression on CD4 T cells from the SLE patients was correlated with CD154 message and transcription rates by real‐time reverse transcription–polymerase chain reaction (RT‐PCR) and nuclear run‐on assays, respectively. Nuclear factor of activated T cell (NF‐AT) transcription activity and mRNA levels in CD4 T cells from SLE patients were explored by reporter gene analysis and real‐time RT‐PCR, respectively. Results CD154 surface protein levels were increased 1.44‐fold in CD4 T cells from SLE patients as compared with controls in cells evaluated 1 day postactivation ex vivo. This increase correlated clinically with the presence of nephritis and an elevated erythrocyte sedimentation rate. Increased CD154 protein levels also correlated with increased CD154 mRNA levels and with CD154 transcription rates, particularly at later time points following T cell activation. Reporter gene analyses revealed a trend for increased NF‐AT, but decreased activator protein 1 and similar NF‐κB, activity in CD4 T cells from SLE patients as compared with controls. Moreover, NF‐AT1 and, in particular, NF‐AT2 mRNA levels were notably increased in CD4 T cells from SLE patients as compared with controls. Conclusion Following activation, cell surface CD154 is increased on CD4 T cells from pediatric lupus patients as compared with controls, and this increase correlates with the presence of nephritis, increased CD154 transcription rates, and increased NF‐AT activity. These results suggest that NF‐AT/calcineurin inhibitors, such as tacrolimus and cyclosporine, may be beneficial in the treatment of lupus nephritis.Keywords
This publication has 56 references indexed in Scilit:
- FOXP3 Inhibits Activation-Induced NFAT2 Expression in T Cells Thereby Limiting Effector Cytokine ExpressionPublished by The American Association of Immunologists ,2009
- Calcium signaling in systemic lupus erythematosus lymphocytes and its therapeutic exploitationArthritis & Rheumatism, 2008
- Tacrolimus vs. clobetasol propionate in the treatment of facial cutaneous lupus erythematosus: a randomized, double-blind, bilateral comparison studyBritish Journal of Dermatology, 2007
- CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosusClinical and Experimental Immunology, 2006
- Delineation of a Novel Pathway That Regulates CD154 (CD40 Ligand) ExpressionMolecular and Cellular Biology, 2003
- A T Cell-specific Enhancer of the Human CD40 Ligand GenePublished by Elsevier BV ,2002
- TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and FunctionAnnual Review of Immunology, 1997
- The CD40L Promoter Contains Nuclear Factor of Activated T Cells-binding Motifs Which Require AP-1 Binding for Activation of TranscriptionPublished by Elsevier BV ,1996
- Derivation of the sledai. A disease activity index for lupus patientsArthritis & Rheumatism, 1992
- Effects of cyclosporine in severe systemic lupus erythematosusThe Journal of Pediatrics, 1987