TY - JOUR
T1 - Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus
AU - Nansen, A
AU - Jensen, Teis
AU - Christensen, Jan Pravsgaard
AU - Ørding Andreasen, Susanne
AU - Röpke, C
AU - Marker, O
AU - Thomsen, Allan Randrup
N1 - Keywords: Adoptive Transfer; Animals; Hepatitis, Viral, Animal; Interferon-gamma; Liver; Lymphocyte Depletion; Lymphocytic Choriomeningitis; Membrane Glycoproteins; Mice; Mice, Knockout; Perforin; Pore Forming Cytotoxic Proteins; T-Lymphocytes, Cytotoxic; Wasting Syndrome
PY - 1999
Y1 - 1999
N2 - To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus-specific TCR are adoptively transferred before virus challenge, indicating that the disease is the result of an unfortunate balance between virus replication in internal organs, e.g., liver and spleen, and the host response; resetting this balance by increasing host responsiveness will again lead to a rapidly controlled infection and limited tissue damage. Thus, the presence or absence of IFN-gamma determines whether CTLs will clear infection with this noncytopathogenic virus or induce severe immunopathology.
AB - To define the role of IFN-gamma in the control of acute infection with a noncytopathogenic virus, mice with targeted defects of the genes encoding IFN-gamma, perforin, or both were infected i.v. with two strains of lymphocytic choriomeningitis virus differing markedly in their capacity to spread in wild-type mice. Our results reveal that IFN-gamma is pivotal to T cell-mediated control of a rapidly invasive stain, whereas it is less important in the acute elimination of a slowly invasive strain. Moreover, the majority of mice infected with the rapidly invasive strain succumb to a wasting syndrome mediated by CD8+ effector cells. The primary effector mechanism underlying this disease is perforin-dependent lysis, but other mechanisms are also involved. Wasting disease can be prevented if naive CD8+ cells from mice transgenic for an MHC class I-restricted lymphocytic choriomeningitis virus-specific TCR are adoptively transferred before virus challenge, indicating that the disease is the result of an unfortunate balance between virus replication in internal organs, e.g., liver and spleen, and the host response; resetting this balance by increasing host responsiveness will again lead to a rapidly controlled infection and limited tissue damage. Thus, the presence or absence of IFN-gamma determines whether CTLs will clear infection with this noncytopathogenic virus or induce severe immunopathology.
M3 - Journal article
C2 - 10570301
SN - 0022-1767
VL - 163
SP - 6114
EP - 6122
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -