The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells. Further, the number of autoreactive liver-infiltrating CD4 and CD8 cells is significantly higher in liver than blood in patients with PBC. Based on this data, we have studied the frequencies and phenotypic characterization of both CD4 and CD8 regulatory T cell components in both patients with PBC and age-sex matched controls. Our data is striking and indicate that CD8 Treg populations from PBC patients, but not controls, have significant phenotypic alterations, including increased expression of CD127 and reduced CD39. Furthermore, in vitro induction of CD8 Tregs by incubation with IL10 is significantly reduced in PBC patients. Importantly, the frequencies of circulating CD4+CD25+ and CD8+ and CD28- T cell subpopulations are not significantly different between patients and controls. In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC. © 2010 Elsevier Ltd

Bernuzzi, F., Fenoglio, D., Battaglia, F., Fravega, M., Gershwin, M., Indiveri, F., et al. (2010). Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis. JOURNAL OF AUTOIMMUNITY, 35(3), 176-180 [10.1016/j.jaut.2010.06.004].

Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis

Bernuzzi, Francesca Veronica;INVERNIZZI, PIETRO;
2010

Abstract

The mechanisms that lead to loss of tolerance in autoimmune disease have remained both elusive and diverse, including both genetic predisposition and generic dysregulation of critical mononuclear cell subsets. In primary biliary cirrhosis (PBC), patients exhibit a multilineage response to the E2 component of pyruvate dehydrogenase involving antibody as well as autoreactive CD4 and CD8 responses. Recent data from murine models of PBC have suggested that a critical mechanism of biliary destruction is mediated by liver-infiltrating CD8 cells. Further, the number of autoreactive liver-infiltrating CD4 and CD8 cells is significantly higher in liver than blood in patients with PBC. Based on this data, we have studied the frequencies and phenotypic characterization of both CD4 and CD8 regulatory T cell components in both patients with PBC and age-sex matched controls. Our data is striking and indicate that CD8 Treg populations from PBC patients, but not controls, have significant phenotypic alterations, including increased expression of CD127 and reduced CD39. Furthermore, in vitro induction of CD8 Tregs by incubation with IL10 is significantly reduced in PBC patients. Importantly, the frequencies of circulating CD4+CD25+ and CD8+ and CD28- T cell subpopulations are not significantly different between patients and controls. In conclusion, these data identify the CD8 Treg subset as a regulatory T cell subpopulation altered in patients with PBC. © 2010 Elsevier Ltd
Articolo in rivista - Articolo scientifico
Autoimmune cholangitis CD8 T regulatory cells; CD39; IL7-R; Adult; Aged; Antigens, CD; Apyrase; CD8-Positive T-Lymphocytes; Cell Count; Cell Movement; Cells, Cultured; Female; Humans; Immunophenotyping; Interleukin-10; Interleukin-7 Receptor alpha Subunit; Liver; Liver Cirrhosis, Biliary; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes, Regulatory; Immunology; Immunology and Allergy
English
176
180
5
Bernuzzi, F., Fenoglio, D., Battaglia, F., Fravega, M., Gershwin, M., Indiveri, F., et al. (2010). Phenotypical and functional alterations of CD8 regulatory T cells in primary biliary cirrhosis. JOURNAL OF AUTOIMMUNITY, 35(3), 176-180 [10.1016/j.jaut.2010.06.004].
Bernuzzi, F; Fenoglio, D; Battaglia, F; Fravega, M; Gershwin, M; Indiveri, F; Ansari, A; Podda, M; Invernizzi, P; Filaci, G
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/106408
Citazioni
  • Scopus 59
  • ???jsp.display-item.citation.isi??? 55
Social impact