Th cell-deficient mice control influenza virus infection more. effectivelythan Th- and B cell-deficient mice: Evidence for a Th-independent contribution by B cells to virus clearance

The notion that MHC class I- restricted CD8(+) T (Tc) cells are capable of resolving autonomously infections with influenza virus is based largely on studies testing virus strains of low pathogenicity in CD4(+) T (Th) cell-de ficient/depleted mice. To test whether this holds also for pathogenic strai ns and to exclude possible contributions by B cells, we analyzed PR8 infect ion in Th cell-depleted B cell-deficient (mu MT) mice. These mice, termed m u MT (-CD4), showed 80% mortality after infection with a small dose of PR8, which resulted in insignificant mortality in intact or Th cell-depleted BA LB/c mice, Infection of mu MT(-CD4) mice with a virus of low pathogenicity was resolved without mortality, but, compared with intact BALB/c mice, with delay of similar to 5 and similar to 20 days from lung and nose, respectiv ely. The low mortality of Th cell-depleted BALB/c mice suggested that Il ce lls contributed to recovery in a Th-independent manner. This was verified b y showing that transfer of 8-10 million T cell-depleted naive spleen cells into mu MT(-CD4) mice 1 day before infection reduced mortality to 0%, The m echanism by which B cells improved recovery was investigated. We found no e vidence that they operated by improving the lung-associated Tc response. Tr eatment of infected mu MT(-CD4) mice with normal mouse serum spiked with he magglutinin-specific IgM did not reduce mortality. Taken together, the data show that 1) the Tc response is capable of resolving autonomously tin conj unction with innate defenses) influenza virus infections, although with sub stantial delay compared with intact mice, and 2) B cells can contribute to recovery by a Th-independent mechanism.