Antivirus antibody-dependent cell-mediated cytotoxicity during murine cytomegalovirus infection.

BALB/c mice infected with murine cytomegalovirus were studied to determine whether antibody-dependent cell-mediated cytotoxicity contributes to the immune control of this infection. Antibody-dependent killer cells from uninfected mice were used as effector cells to assay for antibody in sera of infected mice. Secondary immune sera were found to contain both cytomegalovirus-specific and autoreactive antibodies. After primary infection only cytomegalovirus-specific antibodies were found. These were detected by antibody-dependent cell-mediated cytotoxicity within 8 to 10 days after onset of infection, but usually not until day 21, by a neutralizing antibody assay. Antibody titers were about 10-fold higher by antibody-dependent cell-mediated cytotoxicity than by neutralization. The results indicate that cellular immunity to cytomegalovirus infection includes an antibody-dependent cell-mediated cytotoxicity response which is likely to be highly efficient and may contribute significantly to control of both acute and later stages of infection.

Role of cytotoxic T lymphocytes in murine cytomegalovirus infection.

Cell-mediated immunity is important in host control of CMV infection. A chromium release microcytoxicity assay was used to evaluate the role of cytotoxic T lymphocytes (CTL) in murine CMV infection. Within a few days after intranasal inoculation virus was detected in cultures of buffy-coat, spleens, anterior cervical lymph nodes and salivary glands. CTL were first detected on day 5 post-infection in spleen and peripheral blood, and on day 6 in anterior cervical nodes. The course of the CTL response approximated to that of virus titres during the acute phase of infection in the spleen and blood. The findings indicate that CTL are distributed to infected tissues and appear to be important during the acute, viraemic phase of infection.

The role of natural killer cells and antibody-dependent cell-mediated cytotoxicity during murine cytomegalovirus infection.

Definition of the functions by which the cellular immune system contributes to control of cytomegalovirus (CMV) infection should permit determination of the specific defects which result in the increased susceptibility to infection of immunosuppressed individuals. Using a murine model, we studied the cytotoxic lymphocyte response to murine CMV infection. This response was found to be biphasic. The initial phase extended from the 3rd to the 6th d after infection, was not genetically restricted, and correlated to a rise in numbers of natural killer (NK) and antibody-dependent killer (K) cells in spleens. The NK- and K-cell responses were preceded, by 24 h, by a rise in serum interferon levels, and occurred before the time when antibody could be measured in serum by neutralization. NK and K cells appear to develop the capacity for specific recognition of CMV-infected cells and the potential to contribute to control of the acute phase of CMV infection.

Latent cytomegalovirus infection of BALB/c mouse spleens detected by an explant culture technique.

Latent murine cytomegalovirus (MCMV) infection of BALB/c mouse spleens was studied using several methods including an explant tissue culture technique, co-cultivation on allogeneic and syngeneic cell cultures and nucleic acid hybridization. BALB/c mice experience latent infection which persists for at least 6 months and involves only a small fraction of spleen cells. The explant culture technique proved to be much more sensitive than other methods for detecting latent infection of lymphoid tissues.

Correlation of laboratory studies with clinical responses to A/New Jersey influenza vaccines.

The large, uniformly performed clinical investigations with influenza A/New Jersey vaccines provided an opportunity to correlate results of laboratory tests of vaccine with human reactivity and antibody responses. These vaccines were given to large numbers of subjects under code, and significant differences in immunogenicity and reactivity were observed in unprimed individuals. A single, relatively large dose of intact virus was more immunogenic and reactive than split-virus vaccines in unprimed subjects. Differences in immunogenicity and reactivity in unprimed subjects correlated with the amount of intact virus in the vaccines (measured by column chromatography or electron microscopy) and with the amount of viral hemagglutinin in the vaccine (measured by immunodiffusion), but not with the number of chick cell-agglutinating units.

The effect of mycoplasmas on replication and plaquing ability of Herpes simplex virus.

M. arginini, an arginine utilizer, can decrease the yield of Herpes simplex virus, type 1 grown in Vero cells. M. arginini can also cause a reduction in number and size of plaques produced by HSV. The reduction in titer and plaque size produced in M. arginini-infected cells can be reversed by supplementing medium with additional arginine. A. laidlawii, a nonarginine utilizing mycoplasma, had no effect on the growth of HSV.