Cutting Edge: Contribution of Lung-Resident T Cell Proliferation to the Overall Magnitude of the Antigen-Specific CD8 T Cell Response in the Lungs following Murine Influenza Virus Infection

Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
The Journal of Immunology (Impact Factor: 4.92). 10/2009; 183(7):4177-81. DOI: 10.4049/jimmunol.0901109
Source: PubMed


Following influenza virus infection, CD8 T cells encounter mature, Ag-bearing dendritic cells within the draining lymph nodes and undergo activation, programmed proliferation, and differentiation to effector cells before migrating to the lungs to mediate viral clearance. However, it remains unclear whether CD8 T cells continue their proliferation after arriving in the lungs. To address this question, we developed a novel, in vivo, dual-label system using intranasal CFSE and BrdU administration to identify virus-specific CD8 T cells that are actively undergoing cell division while in the lungs. With this technique we demonstrate that a high frequency of virus-specific CD8 T cells incorporate BrdU while in the lungs and that this lung-resident proliferation contributes significantly to the magnitude of the Ag-specific CD8 T cell response following influenza virus infection.

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    • "Inflammatory monocyte-derived DCs arrive in the inflamed lung at the same time as Teff and function as lung APCs, amplifying the inflammatory milieu and locally expanding the emigrating Teff (44). Additionally, CD8+ T cell proliferation continues in the lung, a process requisite for viral control after influenza infection (45). This additional expansion, however, is not without a cost. "
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    • "T cell proliferation is not restricted to lymphoid organs, because T cell proliferation was also found, e.g., at sites of viral infection [98, 99, 118–121]. In influenza infection, proliferating T cells in the lungs contribute substantially to the total number of cytotoxic T-cells in the lung [98, 118]. Also, the persistence and reactivation of influenza-specific CD8+ memory T-cells can take place in mice without secondary lymphoid organs [119]. "
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    • "Even after leaving the central lymphoid organs and trafficking via the blood to the peripheral site of infection, CD8 + effector CTL continue to engage in antigen-specific interactions that (apart from resulting in cytolysis of infected targets) drive further proliferation and cytokine release. A combination of local CFSE and BrdU administration reveals extensive continued proliferation of newly arrived CTL in the lung contributing substantially to the overall magnitude of the response to influenza infection (Bedoui and Gebhardt, 2011; McGill and Legge, 2009). The greatest on-site proliferation coincides with the appearance in the lung on monocyte-derived inflammatory DCs. "
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