| First Author | Trautmann T | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 1 | Pages | e86348 |
| PubMed ID | 24466045 | Mgi Jnum | J:212565 |
| Mgi Id | MGI:5581774 | Doi | 10.1371/journal.pone.0086348 |
| Citation | Trautmann T, et al. (2014) CD4+ T-cell help is required for effective CD8+ T cell-mediated resolution of acute viral hepatitis in mice. PLoS One 9(1):e86348 |
| abstractText | 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-gamma 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. |
