CD4+ T-cell help is required for effective CD8+ T cell-mediated resolution of acute viral hepatitis in mice
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CD4+ T-cell help is required for effective CD8+ T cell-mediated resolution of acute viral hepatitis in mice. / Trautmann, Tanja; Kozik, Jan-Hendrik; Carambia, Antonella; Richter, Kirsten; Lischke, Timo; Schwinge, Dorothee; Mittrücker, Hans-Willi; Lohse, Ansgar W; Oxenius, Annette; Wiegard, Christiane; Herkel, Johannes.
In: PLOS ONE, Vol. 9, No. 1, 01.01.2014, p. e86348.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - CD4+ T-cell help is required for effective CD8+ T cell-mediated resolution of acute viral hepatitis in mice
AU - Trautmann, Tanja
AU - Kozik, Jan-Hendrik
AU - Carambia, Antonella
AU - Richter, Kirsten
AU - Lischke, Timo
AU - Schwinge, Dorothee
AU - Mittrücker, Hans-Willi
AU - Lohse, Ansgar W
AU - Oxenius, Annette
AU - Wiegard, Christiane
AU - Herkel, Johannes
PY - 2014/1/1
Y1 - 2014/1/1
N2 - Cytotoxic CD8+ T cells are essential for the control of viral liver infections, such as those caused by HBV or HCV. It is not entirely clear whether CD4+ T-cell help is necessary for establishing anti-viral CD8+ T cell responses that successfully control liver infection. To address the role of CD4+ T cells in acute viral hepatitis, we infected mice with Lymphocytic Choriomeningitis Virus (LCMV) of the strain WE; LCMV-WE causes acute hepatitis in mice and is cleared from the liver by CD8+ T cells within about two weeks. The role of CD4+ T-cell help was studied in CD4+ T cell-lymphopenic mice, which were either induced by genetic deficiency of the major histocompatibility (MHC) class II transactivator (CIITA) in CIITA-/- mice, or by antibody-mediated CD4+ cell depletion. We found that CD4+ T cell-lymphopenic mice developed protracted viral liver infection, which seemed to be a consequence of reduced virus-specific CD8+ T-cell numbers in the liver. Moreover, the anti-viral effector functions of the liver-infiltrating CD8+ T cells in response to stimulation with LCMV peptide, notably the IFN-γ production and degranulation capacity were impaired in CIITA-/- mice. The impaired CD8+ T-cell function in CIITA-/- mice was not associated with increased expression of the exhaustion marker PD-1. Our findings indicate that CD4+ T-cell help is required to establish an effective antiviral CD8+ T-cell response in the liver during acute viral infection. Insufficient virus control and protracted viral hepatitis may be consequences of impaired initial CD4+ T-cell help.
AB - Cytotoxic CD8+ T cells are essential for the control of viral liver infections, such as those caused by HBV or HCV. It is not entirely clear whether CD4+ T-cell help is necessary for establishing anti-viral CD8+ T cell responses that successfully control liver infection. To address the role of CD4+ T cells in acute viral hepatitis, we infected mice with Lymphocytic Choriomeningitis Virus (LCMV) of the strain WE; LCMV-WE causes acute hepatitis in mice and is cleared from the liver by CD8+ T cells within about two weeks. The role of CD4+ T-cell help was studied in CD4+ T cell-lymphopenic mice, which were either induced by genetic deficiency of the major histocompatibility (MHC) class II transactivator (CIITA) in CIITA-/- mice, or by antibody-mediated CD4+ cell depletion. We found that CD4+ T cell-lymphopenic mice developed protracted viral liver infection, which seemed to be a consequence of reduced virus-specific CD8+ T-cell numbers in the liver. Moreover, the anti-viral effector functions of the liver-infiltrating CD8+ T cells in response to stimulation with LCMV peptide, notably the IFN-γ production and degranulation capacity were impaired in CIITA-/- mice. The impaired CD8+ T-cell function in CIITA-/- mice was not associated with increased expression of the exhaustion marker PD-1. Our findings indicate that CD4+ T-cell help is required to establish an effective antiviral CD8+ T-cell response in the liver during acute viral infection. Insufficient virus control and protracted viral hepatitis may be consequences of impaired initial CD4+ T-cell help.
U2 - 10.1371/journal.pone.0086348
DO - 10.1371/journal.pone.0086348
M3 - SCORING: Journal article
C2 - 24466045
VL - 9
SP - e86348
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 1
ER -