BACKGROUND/AIMS: CD4(+) lymphocytes constitutively expressing the IL-2-receptor alpha-chain (CD25) regulate the activation of CD4 and CD8 autoreactive T-cells by suppressing their proliferation and effector function. The aim of this study is to: (1) measure the percentage of CD4(+)CD25(+) T-cells (T-regs) in patients with autoimmune liver disease at presentation and during remission, (2) correlate their frequency with disease activity, (3) determine their ability to expand and (4) to inhibit interferon-gamma (IFNgamma) production by CD4(+)CD25- T-cells. METHODS: 41 patients were studied. Percentage of T-regs was determined on peripheral blood mononuclear cells (PBMCs) by triple-colour flow cytometry; their ability to expand by exposing PBMCs to a T-cell expander (CD3/CD28 Dynabeads); their immunoregulatory function by measuring their ability to suppress IFNgamma production by CD4(+)CD25(-) T-cells. RESULTS: T-regs were significantly less in patients than in controls, and at diagnosis than during remission. Their percentage was inversely correlated with titres of anti-liver kidney microsomal and soluble liver antigen autoantibodies. T-regs ability to expand was significantly lower in patients than in controls, but that to suppress IFNgamma production by CD4(+)CD25(-) T-cells was maintained. CONCLUSIONS: Decreased T-regs numbers and ability to expand may favour the emergence of liver-targeted autoimmunity, despite preserved suppressor function. Treatment should aim at increasing T-regs number.
BACKGROUND/AIMS: CD4(+) lymphocytes constitutively expressing the IL-2-receptor alpha-chain (CD25) regulate the activation of CD4 and CD8 autoreactive T-cells by suppressing their proliferation and effector function. The aim of this study is to: (1) measure the percentage of CD4(+)CD25(+) T-cells (T-regs) in patients with autoimmune liver disease at presentation and during remission, (2) correlate their frequency with disease activity, (3) determine their ability to expand and (4) to inhibit interferon-gamma (IFNgamma) production by CD4(+)CD25- T-cells. METHODS: 41 patients were studied. Percentage of T-regs was determined on peripheral blood mononuclear cells (PBMCs) by triple-colour flow cytometry; their ability to expand by exposing PBMCs to a T-cell expander (CD3/CD28 Dynabeads); their immunoregulatory function by measuring their ability to suppress IFNgamma production by CD4(+)CD25(-) T-cells. RESULTS: T-regs were significantly less in patients than in controls, and at diagnosis than during remission. Their percentage was inversely correlated with titres of anti-liver kidney microsomal and soluble liver antigen autoantibodies. T-regs ability to expand was significantly lower in patients than in controls, but that to suppress IFNgamma production by CD4(+)CD25(-) T-cells was maintained. CONCLUSIONS: Decreased T-regs numbers and ability to expand may favour the emergence of liver-targeted autoimmunity, despite preserved suppressor function. Treatment should aim at increasing T-regs number.
Authors: A Perrella; L Vitiello; L Atripaldi; P Conti; C Sbreglia; S Altamura; T Patarino; R Vela; G Morelli; P Bellopede; C Alone; L Racioppi; O Perrella Journal: Gut Date: 2006-09 Impact factor: 23.059
Authors: Michael W Milks; James G Cripps; Heping Lin; Jing Wang; Richard T Robinson; Jennifer L Sargent; Michael L Whitfield; James D Gorham Journal: Liver Int Date: 2009-04-16 Impact factor: 5.828