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T-lymphocyte effects on murine cytomegalovirus pulmonary infection
M Kadima-Nzuji1, J E Craighead
1Department of Pathology, University of Vermont, College of Medicine, Burlington 05405.
Abstract:
Cytomegalovirus (CMV) infections were induced in male BALB/c mice treated with rat monoclonal antibodies (MAb) to deplete selectively CD8 and CD4 cell populations in vivo. The animals were then inoculated intraperitoneally with murine CMV and the infection was monitored virologically and histologically. High concentrations of virus were found in the lungs of mice depleted of CD4 or both CD4 and CD8 cells. These animals developed pulmonary infections that persisted for at least 49 days after inoculation. In contrast, immunologically intact mice and those administered anti-CD8 MAb experienced only a transient infection of the lungs. Focal interstitial infiltrates of mononuclear cells were demonstrated in pulmonary tissues of CD4 MAb-treated animals, but not in normal mice and those receiving the CD8 MAb. Adoptive transfer of CD4 cells to animals (rendered immune-incompetent by thymectomy and irradiation) protected against pulmonary infection and the development of interstitial pneumonia. Mice treated with CD4 MAb failed to produce specific CMV antibody, whereas the depletion of CD8 cells had no effect on antibody elaboration. Administration of anti-CD4 and CD8 MAb did not affect virus replication in the salivary glands, the preferential site for CMV infection in the mouse. Induction of pulmonary infection and interstitial pneumonia by CMV in BALB/c mice is mediated by CD4 T cells.
Insights
Cytomegalovirus (CMV) infection in mice shows CD4 T cells are crucial for persistent lung infections and pneumonia. Depleting these cells prevents antibody production and lung disease.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Cytomegalovirus (CMV) is a common virus with varied clinical manifestations.
- The role of specific T cell subsets in CMV-induced pulmonary disease is not fully understood.
Purpose of the Study:
- To investigate the role of CD4 and CD8 T cells in the pathogenesis of murine CMV (MCMV) pulmonary infection.
- To determine the impact of T cell depletion on viral clearance, lung pathology, and antibody production.
Main Methods:
- BALB/c mice were treated with monoclonal antibodies (MAb) to deplete CD4+ or CD8+ T cells.
- Mice were inoculated with MCMV, and infection was monitored virologically and histologically.
- Adoptive transfer of CD4+ T cells was performed in thymectomized, irradiated mice.
Main Results:
- Depletion of CD4+ T cells, or both CD4+ and CD8+ T cells, led to high viral loads and persistent pulmonary infections.
- CD4+ T cell-depleted mice developed interstitial pneumonia, unlike CD8+ T cell-depleted or intact mice.
- CD4+ T cell depletion abrogated CMV-specific antibody production.
- Adoptive transfer of CD4+ T cells conferred protection against MCMV-induced lung disease.
Conclusions:
- CD4+ T cells are essential mediators of host defense against MCMV pulmonary infection and interstitial pneumonia.
- CD4+ T cells play a critical role in controlling viral replication in the lungs and driving protective immune responses, including antibody production.