Role of T cells in virus control and disease after infection with pneumonia virus of mice.
Infection of mice with pneumonia virus of mice (PVM) is used as a natural host experimental model for studying the pathogenesis of infection with the closely related human respiratory syncytial virus. We analyzed the contribution of T cells to virus control and pathology after PVM infection. Control of a sublethal infection with PVM strain 15 in C57BL/6 mice was accompanied by a 100-fold increase in pulmonary cytotoxic T lymphocytes, 20% of which were specific for PVM. T-cell-deficient mice failed to eliminate PVM and became virus carriers in the absence of the clinical or histopathological signs of pneumonia that occurred after infection of control mice. Mice with limited T-cell numbers did not achieve virus control without weight loss, indicating that T-cell-mediated virus control was closely linked to immunopathology. Both CD4 and CD8 T cells independently contributed to virus elimination and disease. Virus control and disease were similar in the absence of perforin, gamma interferon, or tumor necrosis factor alpha. Interestingly, disease and mortality after lethal high-dose PVM infection were independent of T cells. These data illustrate a key role for T cells in control of PVM infection and demonstrate that both T-cell-dependent and -independent pathways contribute to disease in a viral dose-dependent fashion.
Frey
Stefanie
S
Center for Pediatrics and Adolescent Medicine, University of Freiburg, D-79106 Freiburg, Germany.
Krempl
Christine D
CD
Schmitt-Gräff
Annette
A
Ehl
Stephan
S
D000818:Animals; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus; D054353:Perforin / Q000502:physiology; D018186:Pneumovirus Infections / Q000276:immunology* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014779:Virus Replication; D015431:Weight Loss
D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma