TORNA ALL’ELENCO

CD4+ T-cell responses in churg-strauss syndrome: TH1/TH2 polarization and antigenic targets in European Journal of Immunology

2009
AO Ordine Mauriziano

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (11)Vedi tutti...

Guida G

Martinuzzi E

Boita M


et alii...

Abstract

Objectives: CD4+ T cell abnormalities may play a role in the autoimmune pathogenesis of Churg Strauss Syndrome (CSS). On one side, TH2 (IL-4+) cells may sustain autoantibody formation and eosinophilia, which are hallmarks of CSS. On the other, TH1 (IFN-?+) cells could participate in vessel wall damage and granuloma formation. In order to define this TH1/TH2 balance and to identify potential T cell target antigens (Ags), we analyzed circulating CD4+ T cell responses to polyclonal stimuli and to myeloperoxidase (MPO) in CSS and healthy subjects. Methods: IFN-? and IL-4 expression in peripheral blood CD3+CD4+lymphocytes were measured in 9 CCS patients and 7 healthy subjects (HS) upon polyclonal stimulation, both by intracellular staining and by ELISA. MPO-driven IL-4/IFN-? production was assessed by ELISPOT on T cells co-coltured with autologous dendritic cells, stimulated either with heat-inactivated MPO, negative control protein or hexavalent vaccine (positive control recall Ags). Results: Upon polyclonal stimulation, higher IL-4 and lower IFN-? intracellular expression were detected in CD4+ T cells from CSS patients, as compared to HS (IL-4: 1.3±0.3% vs. 0.50±0.21%, P < 0.05; IFN-?: 14.2±4.5% vs. 27.0±4.8%, P < 0.025). Similar results were obtained by ELISA (IL-4: 0.39±0.16 vs. 0.30±0.07 pg/ml, P < 0.05; IFN-?: 31.0±14.3 vs. 79.0±15.0 pg/ml, P < 0.05). ELISPOT counts of hexavalent vaccine-stimulated CD4+ cells were positive for IL-4 in 4/5 (80%) CSS patients and in 5/5 (100%) HS, and for IFN-? in 2/9 (22%) CSS patients and 7/7 (100%) HS. MPO stimulation determined significant IFN-? release in 5/8 (62%) CSS patients, but not in HS (0/5) No IL-4 response to MPO in both groups was observed. Conclusion: Polyclonally or recall Ag-stimulated CD4+ cells from CSS patients show a TH2-polarized cytokine profile. MPO is here first identified as a CSS-related Ag targeted by CD4+ T cells, and responses towards it are instead TH1-polarized. These data unfol

DOI : 10.1002/eji.200990224

Keywords

diagnosis; immobilization; neoplasm; surgery; protein urine level; nephrotic syndrome; family history; smoking; female; immunology; antiphospholipid syndrome; risk factor; thrombosis; patient; oral contraceptive agent; triacylglycerol; phospholipid antibody; glycoprotein; cardiolipin antibody; chorionic gonadotropin; cholesterol blood level; laboratory; gender; pregnancy; morbidity; laboratory test; hypertension; systolic blood pressure; diastolic blood pressure; obesity; body mass; hyperlipidemia; diabetes mellitus; risk;