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-Deficient Mice Make Delayed, But Effective, T and B Cell Responses to Influenza1
Trudeau Institute, Saranac Lake, NY 12983
Lymphotoxin-
-/- (LT-/-) mice are
thought to be unable to generate effective T and B cell responses. This
is attributed to the lack of lymph nodes and the disrupted splenic
architecture of these mice. However, despite these defects we found
that LT-/- mice could survive infection with a
virulent influenza A virus. LT-/- mice and normal
wild-type mice infected with influenza A generated similar numbers of
influenza-specific CD8 T cells that were able to produce IFN-
and
kill target cells presenting influenza peptides. Furthermore
influenza-infected LT-/- mice produced high titers of
influenza-specific IgM, IgG, and IgA. However, both CD8 and B cell
immune responses were delayed in LT-/- mice by 2–3
days. The delayed cellular and humoral immune response was sufficient
to mediate viral clearance in LT-/- mice that were
infected with relatively low doses of influenza virus. However, when
LT-/- mice were infected with larger doses of
influenza, they succumbed to infection before the immune response was
initiated. These results demonstrate that neither LT nor
constitutively organized lymphoid tissues, such as lymph nodes and
spleen, are absolutely required for the generation of effective
immunity against the respiratory virus influenza A. However, the
presence of LT and/or lymph nodes does accelerate the initiation of
immune responses, which leads to protection from larger doses of
virus.
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