Abstract
Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with 89Zr to image mouse CD8+ T cells in the course of an infection with influenza A virus (IAV). The CD8+ signal showed a strong increase in the mediastinal lymph node (MLN) and thymus as early as 4 days post-infection (dpi), and as early as 6 dpi in the lungs. Over the course of the infection, CD8+ T cells were at first distributed diffusely throughout the lungs and then accumulated more selectively in specific regions of the lungs. These distributions correlated with morbidity as mice reached the peak of weight loss over this interval. CD8+ T cells obtained from control or IAV-infected mice showed a difference in their distribution and migration when comparing their fate upon labeling ex vivo with 89Zr-labeled anti-CD8α nanobody and transfer into infected versus control animals. CD8+ T cells from infected mice, upon transfer, appear to be trained to persist in the lungs, even of uninfected mice. Immuno-PET imaging thus allows noninvasive, dynamic monitoring of the immune response to infectious agents in living animals.
Highlights
We identified the localization of CD8+ T cells from influenza A virus (IAV)-infected and control mice upon transfer to assess cellautonomous migratory behaviors
The agent used for ex vivo labeling of CD8+ T cells prior to use in transfer experiments, as described below, did not include a polyethylene glycol (PEG) moiety
We determined the whole-body distribution of CD8+ T cells in a living mouse in the course of infection with IAV
Summary
Influenza remains a serious disease, with an estimated 1 billion infections per year, some 290,000– 650,000 of which are fatal [1]. Despite the development of antivirals and vaccines, influenza virus-associated deaths remain a major concern. IAV, along with the related influenza B virus, causes a range of clinical manifestations, from mild self-limiting respiratory tract infections, to progressive and sometimes lethal pneumonia [4]. Both the upper and lower respiratory tracts are sites of viral replication, with nascent virions spreading amongst epithelial cells of the upper respiratory tract and trachea in most non-fatal cases. Lower respiratory involvement and pneumonia, caused by the virus and/or secondary bacterial infections, are often seen in fatal cases [5]
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