Protection against influenza virus encephalitis by adoptive lymphocyte transfer

CD8+ cytotoxic T lymphocytes (CTL) have an established role in anti-viral immunity, but whether CTL function efficiently in the brain remains unclear. In particular, virus-infected neurons, which express only low levels of MHC class I antigens and are resistant to the induction of apoptosis, could constitute a relatively intractable CTL target. We have used immune lymphocytes adoptively transferred into the CSF to protect naive mice against an intracerebral infection with influenza A/WSN, a virus that infects neurons in the brain parenchyma and causes a lethal encephalitis. After in vitro restimulation, heterotypically immune spleen cells protected against A/WSN encephalitis in an H-2-restricted, CD8-dependent, CD4-independent manner. Adoptively transferred CTL clones were also protective. Homotypically immune spleen cells additionally mediated CD8-independent, H-2-unrestricted protection, probably due to the generation of A/WSN-specific plasma cells from memory B cells during in vitro restimulation. Thus after in vitro restimulation, either CTL or B cells adoptively transferred into the CSF protected against an acutely lethal intracerebral virus infection.