Cellular Changes in Lungs of Mice Infected with Influenza Virus: Characterization of the Cytotoxic Responses

Abstract

Transpleural lavage of lungs from uninfected C3H mice yielded an average of 300,000 leukocytes per mouse. This number increased eightfold within 6 days after intranasal inoculation with virulent influenza A/Hong Kong/68 (H3N2) virus. Macrophages and lymphocytes in approximately equal numbers comprised 90% or more of the leukocytes both before and during infection. B, T, and null lymphocytes comprised, respectively, 9, 21, and 18% of the leukocytes before infection and 7, 26, and 5% by day 6. In absolute numbers, macrophages and T lymphocytes provided the major increments during infection. Cytotoxic activity of mononuclear cells from lung lavages was compared in a chromium release assay using syngeneic L929 target cells with the activity of mediastinal lymph nodes, spleens, and peripheral blood of uninfected and infected C3H mice. Nonspecific cytotoxicity for target cells infected with H3hkNeql or B/Lee influenza virus was found with mononuclear cells from uninfected mice. This activity tended to be highest with lavage leukocytes and was associated %ith adherent cells, presumably macrophages. Increased virus-specific cytotoxicity was detected with lavage cells by day 6 and persisted through day 9, the period of maximal pneumonia. Similar cytotoxic activity also appeared in cells from the nodes and spleen at this same time but was not detected in peripheral blood cells. The virusspecific cytotoxicity oflavage cells was due largely to a nonadherent cell possessing Fc receptors and theta antigen but lacking C3 receptors; these properties are compatible with actively cytotoxic T lymphocytes. The cytological characteristics of the infiltrating leukocytes and the cytotoxicity data suggest that the local T cell response to influenza virus infection in the lung is a major contributor to the pneumonia observed in this mouse model.

Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection

“…The infiltrated cells produce free radicals and cytokines leading to inflammation in the lungs (Hers et al 1958;Wyde & Cate 1978;Hennet et al 1992aHennet et al , 1992b. The early phase of influenza virus infection is associated with the development of oxidative stress in lung.…”

Comparison of pulmonary diseases in common variable immunodeficiency and X‐linked agammaglobulinaemia

“…62 Cellmediated cytotoxic responses are important in the defence against pulmonary viral infections. 63 It is estimated that about 25% of patients with CVID have moderate CD4 + T lymphopenia, sometimes with a relative expansion of CD8 + T cells. About 30% of patients with CVID have persistently high numbers of circulating CD8 + T cells binding immunogenic peptides from Epstein-Barr virus or cytomegalovirus.…”

The Generation of ‘Cytotoxic’ Macrophages in Mice during Infection with Influenza A or Sendai Virus

“…The level of activity was quite low, however, and it is not possible at present to estimate the relative importance of these cells compared with cytotoxic T cells. However, the lung is relatively rich in macrophages [16], and future work will attempt to quantitate the importance of this mechanism in the control of influenza virus infections.…”