RESISTANCE TO AND RECOVERY FROM LETHAL INFLUENZA-VIRUS INFECTION IN B-LYMPHOCYTE-DEFICIENT MICE

In the adaptive immune response to most viruses, both the cellular and humoral arms of the immune system play complementary roles in elimina ting virus and virus-infected cells and in promoting recovery. To eval uate the relative contribution of CD4(+) and CD8(+) effector T lymphoc ytes in virus clearance and recovery, we have examined the host respon se to lethal type A influenza virus infection in B lymphocyte-deficien t 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 o f influenza, immune B cell-deficient animals show an enhanced resistan ce to lethal virus infection. This finding indicates that an antibody- independent immune-mediated antiviral mechanism accounts for the incre ased resistance to lethal virus challenge. To assess the contribution of influenza-specific CD4(+) and CD8(+) effector T cells in this proce ss, defined clonal populations of influenza-specific CD8(+) and CD8(+) effector T cells were adoptively transferred into lethally infected B cell-deficient mice. Cloned CD8(+) effectors efficiently promoted rec overy from lethal infection, whereas cloned CD4(+) T cells conferred o nly partial protection These results suggest that memory T lymphocytes can act independently of a humoral immune response in order ro confer resistance to influenza infection in immune individuals. The potentia l implications of these results for vaccination against human influenz a infection are discussed.