Characterization of the expanded T-cell populations in patients with Wegener's granulomatosis.
OBJECTIVE
Wegener's granulomatosis (WG) is a chronic inflammatory disease characterized by granulomatosis inflammation, systemic vasculitis and glomerulonephritis. In patients, the peripheral T cells are characterized by mono/oligoclonal CD4+/CD8+ T-cell AV/BV receptor expansions, with aberrant expression of activation markers. This study was designed to characterize the phenotypic differences between the expanded and nonexpanded T-cell populations. Expression of markers for activation, costimulation and adhesion molecules was examined. As earlier studies have shown aberrant expression of CD28/CD152, we also analysed the expression of another costimulatory system, the tumour necrotic factor receptor (TNFR) superfamily proteins.


METHODS
Fluorocrome-conjugated monoclonal antibodies and flow cytometry was used to analyse the expression of the different markers on the surface of the expanded and nonexpanded subsets of T cells.


METHODS
The Karolinska Hospital and Karolinska Institutet in Stockholm, Sweden.


METHODS
Nine patients with WG (six men and three women) had 16 TCRAV/BV CD4+/CD8+ expanded populations that were characterized.


RESULTS
The expanded TCRA/BV CD4+ and CD8+ cells had lower percentages of cells expressing CD28 and higher of those expressing CD152 (CTLA-4). The expanded CD4+ population had more cells expressing HLA-DR, CD57 and CCR5 (CD195), whilst the expression of CD25 was present on fewer of the expanded cells. The expanded CD8+ population contained more cells expressing CD137 (4-1BB), CD137 (4-1BBL), CD30 (Ki-1), CD40 and CD134 (OX40).


CONCLUSIONS
There were marked differences in the phenotypes of expanded and nonexpanded T-cell populations.
Giscombe
R
R
Immunological Research Laboratory, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Wang
X B
XB
Kakoulidou
M
M
Lefvert
A K
AK
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5