Depending on the cytokines present during primary stimulation, CD8 T cells can be polarized into type 1 and type 2 CD8 T cells producing IFN-γ and IL-2 or IL-4, IL-5, IL-6, and IL-10, respectively ( 8– 10). Additional requirements for a CD8 T cell population to be protective against influenza virus infection have not yet been defined.ĬD8 T cells, which were initially described as cytolytic effector cells producing high levels of IFN-γ, have only recently been shown to be a source of a wider variety of cytokines, including both type 1 and type 2 cytokines ( 6, 7). The main effector mechanism of CD8 T cell populations against influenza was shown to be contact–dependent lysis ( 5). The adoptive transfer of influenza virus–immune cytotoxic T cells ( 3) or CD8 T cell clones ( 4) into lethally influenza- infected hosts resulted in a reduction of the pulmonary virus titer and prevention of death. CD8 T cells have been shown to be important effector cells during pulmonary influenza virus infection, promoting host recovery and virus clearance. Thus, the protective value of a CD8 cell population against pulmonary influenza virus infection is strongly correlated with its ability to exert its effector potential at the site of virus infection.Īvariety of factors are involved in the host defense against virus and in the recovery from pulmonary viral infections ( 1, 2). We also show that the expression of several chemokine receptors was selectively regulated in the Tc1 and Tc2 subsets. Tc2 effectors entered the lung with delayed kinetics as compared with Tc1 effectors, and after lung entry Tc2 effector cells did not localize near the infected airway epithelium as did Tc1 effectors but were found within clusters of inflammatory cells distant from the epithelium.
Host recovery mediated by Tc1 effectors was found to be independent of interferon γ production. Cytotoxic T lymphocytes producing type 1 and type 2 cytokine (Tc1 and Tc2) populations were equally cytolytic, but Tc1 effectors and not Tc2 effectors reduced the pulmonary virus titer early during infection. Here we investigated the protective value of defined in vitro–generated hemagglutinin (HA) peptide-specific primary CD8 T cell effectors from the clone 4 T cell receptor transgenic mice, secreting type 1 or type 2 cytokines, against pulmonary infection with whole influenza virus. The requirements for CD8 T cells to provide protection against a localized virus infection in models of adoptive immunotherapy are not well defined.