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.

Rituximab in childhood systemic lupus erythematosus refractory to conventional immunosuppression

“…In accordance with recent findings [12,13], we hypothesized that humoral and cellular immune mechanisms may be fundamentally involved in the pathogenesis of class IV childhood SLE nephritis.…”

cAMP-responsive Element Modulator α (CREMα) trans-Represses the Transmembrane Glycoprotein CD8 and Contributes to the Generation of CD3+CD4−CD8− T Cells in Health and Disease

“…cells are expanded and derive from CD8 ϩ T cells that undergo phenotypic transformation (2)(3)(4)(5), involving the down-regulation of CD8 and the acquisition of a distinct effector phenotype (2,3). Because DN T cells infiltrate tissues, they are believed to be of pathophysiological relevance in SLE (2, 3).…”

“…In SLE, several molecular abnormalities contribute to the proinflammatory phenotype and tissue homing of B and T cells. T cell receptor (TCR)-␣␤ ϩ CD3 ϩ CD4 Ϫ CD8 Ϫ "double-negative" (DN) T cells are expanded in the peripheral blood and infiltrate tissues, where they induce immunoglobulin production and secrete proinflammatory cytokines (2)(3)(4)(5). Recently, we demonstrated that human DN T cells derive from CD8…”

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

“…High levels of human lymphocyte antigen DR (HLA-DR) expression on T cells in SLE patients correlated with severity of disease [59].…”