Recovery from a viral respiratory infection. II. Passive transfer of immune spleen cells to mice with influenza pneumonia.

Abstract The effect of passive transfer of spleen lymphocytes on the course of influenza virus infection in nude and BALB/c mice was investigated. After i.v. administration of labeled normal lymphocytes, more radioactivity and lymphocytes were detected in infected than in uninfected lungs of BALB/c and nude mice, which demonstrated that transferred lymphocytes migrated to the lung during influenza infection. Transfer of nonimmune BALB/c lymphocytes to infected nude mice resulted in a late (day 21) reduction in pulmonary virus titer, but lymphocytes from BALB/c mice infected 8 days previously, which contained some cytotoxic T cell activity, resulted in an earlier and greater reduction in pulmonary virus titers and also helped the antibody response of T cell-deficient recipient mice. Similar but even more dramatic changes in pulmonary virus titer and antibody levels were measured in infected mice receiving splenocytes from immune BALB/c mice 30 or more days after infection or from such cells stimulated secondarily with influenza virus in vitro. Cytotoxic T cell and proliferative responses were measured on days 7 and 14 after infection in recipients of these lymphocytes, and gross microscopic changes in pulmonary pathology and clearance of viral antigens from the lungs were also analyzed. Although the passive transfer of immune lymphocytes markedly enhanced the antibody response, this did not offer significant protection against lethal challenge in nudes or BALB/c mice, nor did nude mice receiving these cells clear virus from the lungs. On the other hand, transfer of these immune lymphocytes after exposure to virus antigen in vitro, which markedly enhanced their cytotoxic T cell activity but did not enhance their effect on antibody levels in recipient mice, did increase recovery from infection and resolution of pneumonia. These results therefore indicate that cytotoxic T lymphocytes are associated with recovery of mice with influenza pneumonia, but immune spleen cells that enhanced antibody responses are not.