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Brief Definitive Reports

Mary Beth Graham^*, and Thomas J. Braciale^*,,||

From the ^* Beirne B. Carter Center for Immunology Research, the Department of Medicine, the Department of Microbiology, and the ^|| Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

In the adaptive immune response to most viruses, both the cellular and humoral arms of the immune system play complementary roles in eliminating virus and virus-infected cells and in promoting recovery. To evaluate the relative contribution of CD4⁺ and CD8⁺ effector T lymphocytes in virus clearance and recovery, we have examined the host response to lethal type A influenza virus infection in B lymphocyte–deficient mice with a targeted disruption in the immunoglobulin mu heavy chain. Our results indicate that naive B cell–deficient mice have a 50– 100-fold greater susceptibility to lethal type A influenza virus infection than do wild type mice. However, after priming with sublethal doses of influenza, immune B cell–deficient animals show an enhanced resistance to lethal virus infection. This finding indicates that an antibody-independent immune-mediated antiviral mechanism accounts for the increased resistance to lethal virus challenge. To assess the contribution of influenza-specific CD4⁺ and CD8⁺ effector T cells in this process, defined clonal populations of influenza-specific CD4⁺ and CD8⁺ effector T cells were adoptively transferred into lethally infected B cell–deficient mice. Cloned CD8⁺ effectors efficiently promoted recovery from lethal infection, whereas cloned CD4⁺ T cells conferred only partial protection. These results suggest that memory T lymphocytes can act independently of a humoral immune response in order to confer resistance to influenza infection in immune individuals. The potential implications of these results for vaccination against human influenza infection are discussed.

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