The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSVinduced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies. (J. Clin. Invest. 1991. 88:1026-1033

A mouse model of respiratory syncytial virus (RSV) infection is described. A high-titered, large-volume inoculum results in replication of RSV to a high titer in lungs of BALB/c mice. Mice older than 15 weeks of age are more susceptible to RSV infection. Titers up to 10(6.9) plaque-forming units (pfu)/gram lung can be attained in 32-week-old mice. Older mice experience a clinical illness manifested by ruffled fur, reduced activity, and weight loss. Lung histology of older mice infected with RSV shows bronchiolitis and increased number of lymphocytes and macrophages in alveolar spaces compared with that of mice less than 8 weeks old. This model will serve as the basis for investigating immunodeterminants of recovery and protection from RSV infection.

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The three major immunocompetent cells in human peripheral blood (lymphocytes, neutrophils, and monocytes) were shown to be effector cells for antibody-dependent cell-mediated cytotoxicity (ADCC) against influenza virus-infected baby hamster kidney cells in vitro. Lymphocyte cytotoxicity was mediated by FcIgG receptor-bearing null cells and T gamma cells. These effector populations were best defined by HNK-1, a monoclonal antibody to human natural killer and ADCC-mediator cells. Antibody responsible for ADCC against influenza virus-infected cells was detectable in sera of young children after natural infection and after vaccination with inactivated and live attenuated viruses. ADCC antibody appeared before hemagglutination-inhibiting antibody and persisted for at least one year after vaccination with live attenuated vaccine. ADCC antibody was subtype-specific but quite broadly reactive within a subtype. Both hemagglutinin and neuraminidase were antigenic determinants for ADCC antibody. An anamnestic response to the original strain was observed after challenge with influenza virus of a heterologous subtype.