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DNA Vaccines: Influenza Virus Challenge of a Th2/Tc2 Immune Response Results in a Th2/Tc1 Response in the Lung

Emory Vaccine Center,¹ Department of Microbiology and Immunology, Emory University School of Medicine,³ Yerkes National Primate Research Center, Emory University, Atlanta, Georgia²

Received 24 September 2003/ Accepted 10 December 2003

For this study, we used DNA-based immunizations to elicit gamma interferon-producing (Tc1) or interleukin 4 (IL-4)-producing (Tc2) CD8 T cells to the influenza virus nucleoprotein. We examined the response of these cells to an intranasal viral challenge. Both the Tc2- and Tc1-biased responses were present in mice with predominantly IL-4-producing (Th2) CD4 T cells. After viral challenge, Tc1 cells underwent more efficient expansion than did Tc2 cells, and only Tc1 cells were detected at the site of infection. In contrast, the CD4 response remained IL-4 biased. However, only a limited number of CD4 cells appeared in the postchallenge lung, and these were strongly enriched for the Th1 phenotype. Thus, the type of memory T-cell response induced by DNA vaccination does not determine the type of response that will predominate at the site of an infection.