Abstract Cytotoxic CD8 + T cells are key mediators of viral clearance during primary infection through their production of IFN‐γ and lysis of virally infected cells. Comparatively, the cytokines IL‐4 and IL‐13 are typically associated with the development of Th2 immune responses against allergens and parasites, while their influence on cytotoxic CD8 + T cell responses is controversial. We have investigated the roles of IL‐4 and IL‐13 in the development of CD8 + T cell responses against influenza infection. We show that in the absence of either IL‐4 or IL‐13, CD8 + T cells proliferated and a normal secondary cytotoxic response developed in vitro . In striking contrast, the absence of IL‐4Rα resulted in impaired ex vivo proliferation and consequently no secondary CTL activity, whereas the in vivo response appeared normal. We show that the presence of CD4 + T cell help, or the addition of exogenous IL‐2 in vitro , restored the response. Taken together, this work reveals previously unrecognized in vivo redundancies between IL‐4, IL‐13 and IL‐2 during immune responses against influenza virus.
Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, recent studies have uncovered key mechanisms through which they contribute to organ homeostasis and immunity. It has also become clear that dysregulation of such interactions is implicated in the development of chronic lung diseases. This review describes the characteristics of the lung nervous system and discusses the molecular mechanisms that underlie lung neuroimmune interactions in infection and disease. We have contextualized the current literature and identified opportune areas for further investigation. Indeed, both the lung-brain axis and local neuroimmune interactions hold enormous potential for the exploration and development of novel therapeutic strategies targeting lung diseases.
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