Influenza virus neuraminidase alters allogeneic T cell proliferation

Influenza virus elicits good cellular and humoral immune responses. Unlike the cytotoxic T lymphocyte response to many other antigens, the cytotoxic T lymphocyte response to influenza virus is CD4(+) T cell independent, suggesting that viral infection of antigen-presenting cells may alter their capacity to stimulate T cell responses. To clarify the role of influenza virus in these functional alterations, we compared T cell responses to uninfected and A/PR/8/34-infected dendritic cells (DC). DC were prepared from the bone marrow of C57BL/6 (H2(b)) mice and used to stimulate in vivo and in vitro alloreactive T cell responses. In both cases, influenza virus infection increased the capacity of DC to stimulate T cell proliferation. This enhancement was blocked by antibodies specific for neuraminidase (NA), but not hemagglutinin. Infection was not required to observe enhanced T cell proliferation, showing that NA from exogeneous virus particles can facilitate this effect. These results are the first to show that influenza virus alters the capacity of DC to stimulate T cell proliferation through mechanisms mediated by viral NA.