title: Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: activation markers.
abstract: Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and the production of autoantibodies, some of which (antibodies to dsDNA) are thought to be pathogenic. T helper cells drive the production of autoantibodies and the aim of this study is to characterize phenotypically a subpopulation of T cells (the CD3+ CD4- CD8-, double negative (DN) T cells) previously identified as helping to enhance anti-DNA antibodies in patients with SLE. Data were obtained using FACS staining of DN T cells that had been purified from PBMCs by magnetic bead separation. The percentage of TCR alphabeta+ DN T cells was found to be significantly higher in patients with SLE as compared with controls (P = 0.02), although there was no significant increase in total percentage of DN T cells, which includes TCR gammadelta+ cells. Activation markers HLA-DR and CD69, the costimulatory molecule CD28 and CTLA-4 were all expressed on the surface of a higher percentage of DN T cells in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls (HC). More DN T cells from patients with SLE were of CD45RA phenotype than was found in controls, while CD45RO-expressing cells were reduced. In addition, DN T cells from patients with SLE expressed significantly higher levels of HLA-DR (P = 0.006), CD28 (P = 0.05), CTLA4 (P = 0.03) and CD45RA (P = 0.05) on the cell surface than those from the CD4/8 population. Correlation of expression of the markers measured with various parameters of disease activity and severity showed that high levels of HLA-DR expression correlated with high circulating serum C3 (> 0.9 IU/ml), indicating that an activated phenotype is consistent with severe disease.
authors.affiliation: Department of Immunology and Molecular Pathology, Royal Free and University College School of Medicine, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Anand
authors.forename: G S
authors.initials: GS
authors.lastname: Dean
authors.forename: K
authors.initials: K
authors.lastname: Quereshi
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: P M
authors.initials: PM
authors.lastname: Lydyard
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers / Q000032:analysis*; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018796:Immunoconjugates; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000737:chemistry*; D000099192:CD69 Antigens
chemical_list: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015415:Biomarkers; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D060908:CTLA-4 Antigen; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D000099192:CD69 Antigens; C556706:CTLA4 protein, human