title: Complement fragment C3d is colocalized within the lipid rafts of T cells and promotes cytokine production.
abstract: The complement system plays an important role in tissue inflammation and damage in SLE patients. High levels of C3d were detected on the surface of erythrocytes and lymphocytes of SLE patients. The objective of this study was to assess the functional consequences of C3d fragments deposited on the surface membrane of SLE T cells.
  
  
  METHODS
  46 SLE patients, 43 patients with other autoimmune diseases (OAD) and 33 healthy individuals (N) were enrolled in this study. T cells were isolated from peripheral blood and flow cytometry studies were conducted to assess the levels of C3d fragments, Ca++ influx responses and cytokine production. Confocal microscopy was used to study co-localized molecules. Student's t-test was performed to determine statistical significance among study groups.
  
  
  RESULTS
  A significant percentage of the SLE T cells were found to be positive for C3d (13.58 ± 3.92%) when compared with normal T cells (4.52 ± 2.92%) (p < 0.0000547) and T cells from patients with other autoimmune diseases (6.31 ± 4.57%) (p < 0.00513). Peak Ca++ influx responses were significantly higher in C3d- SLE T cells compared with C3d+ SLE T cells (p < 0.011). C3d+ T cells produced significantly more IL-2, IFN-gamma, IL-4 and IL-17. In contrast to the increased production of IL-2 by the C3d+ T cells, the overall SLE T cell population produced less IL-2 when compared with T cells from normal individuals or patients with other autoimmune disease. The C3d fragments were found to be localized within the lipid rafts.
  
  
  CONCLUSIONS
  C3d fragments are localized in the lipid rafts of SLE T cells and contribute to abnormal T cell function by modulating Ca++ influx responses and increased cytokine production.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, USA.
authors.forename: O
authors.initials: O
authors.lastname: Borschukova
authors.forename: Z
authors.initials: Z
authors.lastname: Paz
authors.forename: I C
authors.initials: IC
authors.lastname: Ghiran
authors.forename: C-C
authors.initials: CC
authors.lastname: Liu
authors.forename: A H
authors.initials: AH
authors.lastname: Kao
authors.forename: S
authors.initials: S
authors.lastname: Manzi
authors.forename: J M
authors.initials: JM
authors.lastname: Ahearn
authors.forename: G C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D015933:Complement C3d / Q000378:metabolism*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D015933:Complement C3d; D002118:Calcium