Cytokine production in virus-infected mice: a single cell analysis

Antiviral activity of IFN-gamma and TNF has been demonstrated in vitro and in vivo. Recombinant vaccinia viruses that encode either of these cytokines are highly attenuated in vivo and, indeed, are no longer lethal when they are used to infect athymic nude mice. Thus, these cytokines are able to replace the requirement for CD8 T cells in immunodeficient mice. We believe that the antiviral properties of some cytokines are a central component in the physiological control of virus infection. In this report, we used flow cytofluorimetric analysis to simultaneously detect cytokine production and T cell phenotype. Importantly, this method allowed the analysis of cytokine production in cells freshly isolated from tissues. In contrast to other procedures, restimulation of the cells in vitro was not necessary. We demonstrate that CD8 IFN-gamma+ cells were predominantly induced early in the response to vaccinia virus infection and, at the cellular peak of the response, CD8 IFN-gamma+ and CD4 TNF+ T cells were present at equal frequencies. Hence, these findings support the concept that effector T cells produce cytokines that are known to be antiviral, and that these cytokines are an important component of effector T cell activity.