title: T lymphocytes in patients with primary vasculitis: expansion of CD8+ T cells with the propensity to activate polymorphonuclear neutrophils.
abstract: OBJECTIVE
  To gain insight into the immune pathogenesis of primary ANCA-associated vasculitides, the prevalence of circulating T lymphocytes expressing CD11b as a marker for activation was analysed in patients with WG or microscopic polyangiitis. METHODS; Receptor expression and IFNgamma synthesis were measured in T cells of patients with active disease by cytofluorometry and compared with expression in patients in remission and in healthy donors.
  
  
  RESULTS
  During active disease, a small but conspicuous population of CD8+CD28+CD11b+ was found which produced IFNgamma. In healthy donors and in patients in remission or undergoing immunosuppressive therapy, CD11b was exclusively associated with CD8+CD28- cells, the latter being more frequent in patients with long-lasting or severe disease. In vitro experiments confirmed that CD11b is up-regulated when T cells are activated. After multiple rounds of restimulation, the CD11b expression persists whereas CD28 expression is lost, compatible with the notion that CD8+CD28+CD11b+ represents a transient phenotype in the course of T-cell activation. The IFNgamma-producing T cells activated polymorphonuclear neutrophils (PMN) to express MHC class II, thus generating the same PMN phenotype as in patients with active ANCA-associated vasculitis. A similar PMN phenotype could be generated by cultivation with supernatants of activated T cells or by IFNgamma alone, but not by antibodies to proteinase 3.
  
  
  CONCLUSIONS
  In active primary vasculitis, a small population of CD8+ T cells, identified by the expression of CD11b, expands, producing IFNgamma. These T cells could activate PMN, thus generating a long-living and potentially destructive PMN phenotype.
authors.affiliation: Rheumatology, Department of Endocrinology, Diabetology and Rheumatology, Heinrich-Heine-University of Duesseldorf, Moorenstr 5, 40225 Düsseldorf, Germany. Iking-konert@med.uni-duesseldorf.de
authors.forename: C
authors.initials: C
authors.lastname: Iking-Konert
authors.forename: T
authors.initials: T
authors.lastname: Vogl
authors.forename: B
authors.initials: B
authors.lastname: Prior
authors.forename: C
authors.initials: C
authors.lastname: Wagner
authors.forename: O
authors.initials: O
authors.lastname: Sander
authors.forename: E
authors.initials: E
authors.lastname: Bleck
authors.forename: B
authors.initials: B
authors.lastname: Ostendorf
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.forename: K
authors.initials: K
authors.lastname: Andrassy
authors.forename: G M
authors.initials: GM
authors.lastname: Hänsch
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D039481:CD11b Antigen / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D014890:Granulomatosis with Polyangiitis / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D053146:Myeloblastin / Q000276:immunology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D039481:CD11b Antigen; D018106:CD28 Antigens; D007371:Interferon-gamma; D053146:Myeloblastin