Cytotoxic thymus-derived (T) lymphocytes were readily detected in spleens of mice inoculated intranasally with mouse-adapted A/Port Chalmers (H3N2), A/England (H3N2), A/PR/8 (H0n1), and B/Hong Kong influenza viruses. T-cell-mediated lysis of H-2 compatible target cells infected with the strain of virus used to immunize the mice was considerably higher than lysis of either syngeneic cells infected with a different strain of influenza virus or allogeneic cells infected with the immunizing strain of influenza virus. The findings that cytotoxic lymphocytes can distinguish minor antigenic variants among influenza viruses and that lysis depends on H-2 histocompatibility between lymphocyte and target cell support the concept of dual recognition of visual and H-2 histocompatibility antigens in T-cell-mediated antiviral immunity.
Cytotoxic T cells were detected in the cervical lymph nodes, lungs, spleen, and peripheral blood of mice with influenza. Lymphocytes decreased in the peripheral circulation and increased in the lung during the period of acute inflammation and pneumonia. Peak cytotoxic T-cell activity was present at the time of marked pulmonary infiltration, and it decreased with resolution of the pneumonia. The cytotoxic T cells in the lung were shown to be H-2 restricted and specific for the hemagglutinin of the infecting virus. The results indicate that hemagglutinin specific cytotoxic T cells are (a) induced during influenza infection; (b) they circulate in the blood; (c) they are present in greatest number; and (d) they have their peak cytotoxic effect when pneumonia is most marked. We interpret the results to indicate that specific cytotoxic T cells in the infected target organ are part of the immunological and pathological response to virus infection.
Ferrets were infected with A/Port Chalmers/72 influenza virus and the T- and B-cell responses in the spleen, in lymph nodes draining the upper and lower respiratory tract, and in lung washings were examined in vitro. Lymphocyte responses were measured by using a hemolytic plaque assay for B cells and a proliferation assay for T cells. Virus and antibody levels were measured in respiratory tract washings, and antibody titers were measured in sera from infected animals. Individual B cells secreting specific antibody to A/Port Chalmers/72 virus were detected in regional lymph node and spleen preparations as early as 3 days and as late as 43 days after infection. T-cell assays showed an in vitro response of lymph node cells to A/Port Chalmers/73 virus from day 6 to day 43. Virus was isolated from the respiratory tract up to 7 days after infection. Serum hemagglutination-inhibiting antibody was first detectable on day 6, with maximum titers reached by day 10. These results demonstrated that antibody production and a cellular immune responses were detectable at regional sites at a time when virus was still present and before serum antibody was measured.
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