TY - JOUR
T1 - Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection
AU - Stoop, Jeroen N.
AU - Van Der Molen, Renate G.
AU - Baan, Carla C.
AU - Van Der Laan, Luc J.W.
AU - Kuipers, Ernst J.
AU - Kusters, Johannes G.
AU - Janssen, Harry L.A.
PY - 2005/4
Y1 - 2005/4
N2 - Chronic hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. Regulatory T cells (Treg) can suppress the function of effector T cells and may thus be key players in this impaired immune response. Changes in the functionality or number of Treg could explain the decreased antiviral response in chronic HBV patients. To investigate the role of Treg in chronic HBV infection, we compared the proportional frequency and functionality of Treg in peripheral blood of 50 chronic HBV patients, 23 healthy controls, and 9 individuals with a resolved HBV infection. A higher percentage of Treg, defined as CD4, CD25, CD45RO, and cytotoxic T-lymphocyte-associated antigen 4-positive cells, was detected within the population of CD4+ cells in peripheral blood of chronic HBV patients compared with healthy controls and individuals with a resolved HBV infection. Accordingly, chronic HBV patients displayed a higher FoxP3 messenger RNA level than healthy controls. Depletion of CD25+ cells from peripheral blood mononuclear cells (PBMC) of chronic HBV patients resulted in an enhanced proliferation after stimulation with HBV core antigen. Reconstitution of these depleted PBMC with CD4+CD25+ Treg resulted in a dose-dependent reduction of both HBV-specific proliferation and interferon γ production. In conclusion, chronic HBV patients harbor an increased percent-age of Treg in peripheral blood compared with controls. Treg have an immunosuppressive effect on HBV-specific T helper cells. The presence of HBV-specific Treg could contribute to an inadequate immune response against the virus, leading to chronic infection.
AB - Chronic hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. Regulatory T cells (Treg) can suppress the function of effector T cells and may thus be key players in this impaired immune response. Changes in the functionality or number of Treg could explain the decreased antiviral response in chronic HBV patients. To investigate the role of Treg in chronic HBV infection, we compared the proportional frequency and functionality of Treg in peripheral blood of 50 chronic HBV patients, 23 healthy controls, and 9 individuals with a resolved HBV infection. A higher percentage of Treg, defined as CD4, CD25, CD45RO, and cytotoxic T-lymphocyte-associated antigen 4-positive cells, was detected within the population of CD4+ cells in peripheral blood of chronic HBV patients compared with healthy controls and individuals with a resolved HBV infection. Accordingly, chronic HBV patients displayed a higher FoxP3 messenger RNA level than healthy controls. Depletion of CD25+ cells from peripheral blood mononuclear cells (PBMC) of chronic HBV patients resulted in an enhanced proliferation after stimulation with HBV core antigen. Reconstitution of these depleted PBMC with CD4+CD25+ Treg resulted in a dose-dependent reduction of both HBV-specific proliferation and interferon γ production. In conclusion, chronic HBV patients harbor an increased percent-age of Treg in peripheral blood compared with controls. Treg have an immunosuppressive effect on HBV-specific T helper cells. The presence of HBV-specific Treg could contribute to an inadequate immune response against the virus, leading to chronic infection.
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U2 - 10.1002/hep.20649
DO - 10.1002/hep.20649
M3 - Article
C2 - 15791617
AN - SCOPUS:16244385911
SN - 0270-9139
VL - 41
SP - 771
EP - 778
JO - Hepatology
JF - Hepatology
IS - 4
ER -
