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From the Trudeau Institute, Saranac Lake, New York 12983

The requirements for CD8 T cells to provide protection against a localized virus infection in models of adoptive immunotherapy are not well defined. 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. 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. Host recovery mediated by Tc1 effectors was found to be independent of interferon production. 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. We also show that the expression of several chemokine receptors was selectively regulated in the Tc1 and Tc2 subsets. 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.

Key Words: CD8 • subset • migration • influenza virus • protection

Adelheid Cerwenka was supported by the Schroedinger Stipendium (Project JO111-MED) from the Austrian government. This work was supported in part by National Institutes of Health grants AI7935 and AI36263.

Abbreviations used: HA, hemagglutinin; LT-β, lymphotoxin-β; MDCK cells, Madine Derby canine kidney cells; t₀, before restimulation; TBLN, tracheal bronchial lymph node; Tc1/Tc2, CTLs producing type 1/type 2 cytokines.

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