Increased expression and release of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active disease.
Increased expression of TRAIL in membrane-bound and soluble form in patients with systemic lupus erythematosus (SLE) has been previously reported. In this study, we characterized the upregulation of T-cell-associated and soluble TRAIL (sTRAIL) in vivo and the modulation of TRAIL expression and soluble protein release in vitro following T cell activation and IFNalpha exposure. The expression of membrane-bound TRAIL as determined by flow cytometry was higher on CD4(+) and CD8(+) T cells from lupus patients compared to controls, particularly on activated CD69(+)CD8(+) T cells. Similarly, sTRAIL levels determined by ELISA were significantly elevated in serum from patients with active SLE and correlated with levels of IFNalpha. In vitro, both T-cell-associated and sTRAIL were maximally induced by T cell activation plus IFNalpha in patients and controls. By Western blot analysis, sTRAIL was detected in sera in both the monomeric and multimeric, functional form. Both forms of TRAIL were functional in vitro as determined by Annexin V staining and (51)Cr release assay but the apoptotic activity of membrane TRAIL was 2.5-fold higher compared to that of sTRAIL. These results indicate that IFNalpha-induced enhancement of TRAIL expression and of TRAIL-mediated apoptosis may amplify the abnormal apoptotic process in SLE.
Rus
Violeta
V
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland at Baltimore, 21201, USA. vrus@umaryland.edu
Zernetkina
Valentina
V
Puliaev
Roman
R
Cudrici
Cornelia
C
Mathai
Susan
S
Via
Charles S
CS
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha