Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease.
OBJECTIVE
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.
Longhi
Maria Serena
MS
Institute of Liver Studies, GKT Medical School and King's College Hospital, University of London, London SE5 9RS, UK.
Ma
Yun
Y
Bogdanos
Dimitrios P
DP
Cheeseman
Paul
P
Mieli-Vergani
Giorgina
G
Vergani
Diego
D
D001323:Autoantibodies / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D001323:Autoantibodies; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma