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.

4 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Resident memory T cells (TRM) are broadly defined as a population of T cells, which persist in non-lymphoid sites long-term, do not re-enter the circulation, and are distinct from central memory T cells (TCM) and circulating effector memory T cells (TEM). Recent studies have described populations of TRM cells in the skin, gut, lungs, and nervous tissue. However, it is becoming increasingly clear that the specific environment in which the TRM reside can further refine their phenotypical and functional properties. Here, we focus on the TRM cells that develop following respiratory infection and reside in the lungs and the lung airways. Specifically, we will review recent studies that have described some of the requirements for establishment of TRM cells in these tissues, and the defining characteristics of TRM in the lungs and lung airways. With continual bombardment of the respiratory tract by both pathogenic and environmental antigens, dynamic fluctuations in the local milieu including homeostatic resources and niche restrictions can impact TRM longevity. Beyond a comprehensive characterization of lung TRM cells, special attention will be placed on studies, which have defined how the microenvironment of the lung influences memory T cell survival at this site. As memory T cell populations in the lung airways are requisite for protection yet wane numerically over time, developing a comprehensive picture of factors which may influence TRM development and persistence at these sites is important for improving T cell-based vaccine design.
    Frontiers in Immunology 07/2014; 5:320. DOI:10.3389/fimmu.2014.00320
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research.
    Cellular and Molecular Life Sciences CMLS 02/2013; 70(20). DOI:10.1007/s00018-013-1286-4 · 5.81 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Resting naive CD8(+) T cells have an astounding capacity to react to pathogens by massive expansion and differentiation into cytotoxic effector cells that migrate to all corners of the body to clear the infection. The initial interaction with antigen-presenting cells in the central lymphoid organs drives an orchestrated program of differentiation aimed at producing sufficient numbers of effectors to get the job done without resulting in clonal exhaustion. Interactions with antigen-presenting cells and other immune cells continue at the site of infection to regulate further on-site expansion and differentiation, all with the goal of protecting the host with minimal bystander tissue damage. Here we review recent advances in CD8(+) T cell recognition of antigen in lymphoid as well as in nonlymphoid tissues in the periphery, and how CD8(+) T cell expansion and differentiation are controlled in these contexts.
    Immunity 08/2011; 35(2):161-8. DOI:10.1016/j.immuni.2011.07.010 · 21.56 Impact Factor
Show more


4 Reads
Available from