Lymphotoxin-α-Deficient Mice Make Delayed, But Effective, T and B Cell Responses to Influenza

Abstract

Lymphotoxin-α−/− (LTα−/−) 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 LTα−/− mice could survive infection with a virulent influenza A virus. LTα−/− 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-γ and kill target cells presenting influenza peptides. Furthermore influenza-infected LTα−/− mice produced high titers of influenza-specific IgM, IgG, and IgA. However, both CD8 and B cell immune responses were delayed in LTα−/− mice by 2–3 days. The delayed cellular and humoral immune response was sufficient to mediate viral clearance in LTα−/− mice that were infected with relatively low doses of influenza virus. However, when LTα−/− mice were infected with larger doses of influenza, they succumbed to infection before the immune response was initiated. These results demonstrate that neither LTα 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 LTα and/or lymph nodes does accelerate the initiation of immune responses, which leads to protection from larger doses of virus.

CD8+ T cells responding to influenza infection reach and persist at higher numbers than CD4+ T cells independently of precursor frequency

“…We found high levels of ex vivo CTL activity in cells from the lung and spleen, but little or no activity in cells from the DLN and NDLN. CTL activity in cells from the influenza-infected lung has been reported previously [13,33]. This lack of CTL activity in DLN agrees with Johnson et al [45], but they also found low CTL activity in the spleen.…”

Inhalation Tolerance Is Induced Selectively in Thoracic Lymph Nodes but Executed Pervasively at Distant Mucosal and Nonmucosal Tissues

“…Indeed, while this minute proliferation was observed, our data clearly demonstrated that the absolute number of these cells in distal LNs during Ag aerosolization was extremely small. A number of reports have proposed the lung itself to serve as a site of Ag presentation and primary T cell priming to live replicating Ags (influenza virus infection) through the induction of bronchus-associated lymphoid tissue (65,66). However, the nature of the Ag is likely to be important, as we have previously shown that in mice devoid of LNs and spleen, the lung is unable to evoke Ag-specific primary immune responses to the model Ag, OVA (67).…”

Secondary lymphoid organs are dispensable for the development of T‐cell‐mediated immunity during tuberculosis

“…Similar results were reported in the case of influenza virus infection of LTa-deficient mice, which also lack LN. LTa-deficient mice exhibited delayed immune responses to influenza virus and only survived at low infection doses that allow time for acquired immune responses to develop [29]. Thus, by employing a low MTB dose, we could exploit LTbRxSp-deficient mice as a model lacking SLO despite the demonstrated critical role of lymphotoxin signaling in TB [16,17].…”