Migration kinetics and final destination of type 1 and type 2 CD8 effectorcells predict protection against pulmonary virus infection

The requirements for CD8 T cells to provide protection against a localized virus infection in models of adoptive immunotherapy are not well defined. H ere we investigated the protective value of defined in vitro-generated hema gglutinin (HA) peptide-specific primary CD8 T cell effectors from the clone 4 T cell receptor transgenic mice, secreting type 1 or type 2 cytokines, a gainst pulmonary infection with whole influenza virus. Cytotoxic T lymphocy tes producing type 1 and type 2 cytokine (Tc1 and Tc2) populations were equ ally cytolytic, but Tc1 effecters and not Tc2 effectors reduced the pulmona ry virus titer early during infection. Host recovery mediated by Tc1 effect ers was found to be independent of interferon gamma production. Tc2 effecto rs entered the lung with delayed kinetics as compared with Tc1 effectors, a nd after lung entry Tc2 effector cells did not localize near the infected a irway epithelium as did Tc1 effectors but were found within clusters of inf lammatory cells distant from the epithelium. We also show that the expressi on of several chemokine receptors was selectively regulated in the Tc1 and Tc2 subsets. Thus, the protective value of a CD8 cell population against pu lmonary influenza virus infection is strongly correlated with its ability t o exert its effector potential at the site of virus infection.