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* Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia; and
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105
The development and resolution phases of influenza-specific CD8+ T cell cytokine responses to epitopes derived from the viral nucleoprotein (DbNP366) and acid polymerase (DbPA224) were characterized in C57BL/6J mice for a range of anatomical compartments in the virus-infected lung and lymphoid tissue. Lymphocyte numbers were measured by IFN-
expression following stimulation with peptide, while the quality of the response was determined by the intensity of staining and the distribution of CD8+ T cells producing TNF-
and IL-2. Both the levels of expression and the prevalence of TNF-+ and IL-2+ cells reflected the likely Ag load, with clear differences being identified for populations from the alveolar space vs the lung parenchyma. Irrespective of the site or time of T cell recovery, IL-2+ cells were consistently found to be a subset of the TNF-+ population which was, in turn, contained within the IFN-+ set. The capacity to produce IL-2 may thus be considered to reflect maximum functional differentiation. The hierarchy in cytokine expression throughout the acute phase of the primary and secondary response tended to be DbPA224 > DbNP366. Both elution studies with the cognate tetramers and experiments measuring CD8
coreceptor dependence for peptide stimulation demonstrated the same DbPA224 > DbNP366 profile for TCR avidity. Overall, the quality of any virus-specific CD8+ T cell response appears variously determined by the avidity of the TCR-pMHC interaction, the duration and intensity of Ag stimulation characteristic of the particular tissue environment, and the availability of CD4+ T help.
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