Enhanced survival of lung tissue-resident memory CD8+ T cells during infection with influenza virus due to selective expression of IFITM3

Wakim, Linda M.; Gupta, Nishma; Mintern, Justine D.; Villadangos, José A

doi:10.1038/ni.2525

Cited by 196 publications

(203 citation statements)

References 25 publications

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“…Expression of CD69 and CD103 has been used to identify tissue-resident memory CD8 T cells that have been shown to form stable long-lasting populations in the lung tissue following respiratory viral infections (24)(25)(26)(27). Up to 40% or 50% of the antigen-specific CD8 T cells expressed either CD69 or CD103, respectively, and Ͼ95% of these cells were unlabeled, suggesting that they are tissue-resident memory T cells.…”

Section: Discussionmentioning

confidence: 99%

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

Knudson

Weiss

Hartwig

et al. 2014

J Virol

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The migration of pathogen-specific T cells into nonlymphoid tissues, such as the lung, is critical to control peripheral infections. Use of in vivo intravascular labeling of leukocytes has allowed for improved discrimination between cells located in the blood from cells present within peripheral tissues, such as the lung. This is particularly important in the lung, which is comprised of an intricate network of blood vessels that harbors a large proportion of the total blood volume at any given time. Recent work has demonstrated that >80% of antigen-specific effector CD8 T cells remain in the pulmonary vasculature following an intratracheal infection with a systemic viral pathogen. A n intricate network of blood vessels is associated with the bronchial tree and alveolar sacs of the lung (1). The vascular network is necessary for respiratory function as well as for the trafficking of leukocytes into the lung during infection (2). Leukocytes that remain in the vasculature can be detected by intravenous (i.v.) administration of a specific antibody prior to perfusion and tissue isolation (3-5). Recent work has shown that 80 to 95% of T cell receptor (TCR) transgenic effector and memory CD8 T cells are confined to the pulmonary vasculature following an intratracheal lymphocytic choriomeningitis virus (LCMV) infection despite extensive lung perfusion (4). Importantly, LCMV disseminates systemically even after an intratracheal or intranasal (i.n.) infection. Therefore, it remains unclear what proportion of T cells isolated from a perfused lung are within the lung tissue versus the pulmonary vasculature following an intranasal inoculation with a virus causing a localized respiratory infection.CD8 T cells play a critical role in mediating clearance of acute localized respiratory viral infections such as those caused by respiratory syncytial virus (RSV) and influenza A virus (IAV) (6, 7). Due to the critical role CD8 T cell responses play in mediating the clearance of respiratory viral infections, we sought to determine whether the majority of endogenous virus-specific CD8 T cells were located within lung tissue following a localized pulmonary viral infection. In contrast to systemic infections, our results demonstrate that 80 to 90% of endogenous virus-specific effector and memory CD8 T cells are located within lung tissue following a localized pulmonary viral infection. Furthermore, using cytokine reporter mice, we show that gamma interferon-positive (IFN-␥ ϩ ) endogenous effector CD8 T cells are highly enriched within lung tissue following a respiratory viral infection compared to a systemic infection. These data indicate that the tissue tropism of a virus significantly impacts the localization pattern of virus-specific effector and memory CD8 T cells.

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Section: Discussionmentioning

confidence: 99%

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

Knudson

Weiss

Hartwig

et al. 2014

J Virol

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“…They show polyfunctionality after antigen-independent activation (140, 141), but almost nothing is appreciated about the cytokine profiles, skewing, or other activities of naturally stimulated lung T RM . In mice, lung T RM but not memory cells from secondary lymphoid organs express IFITM3, an antiviral protein permitting cell survival when the lung is infected by influenza virus (143), indicating an adaptation to tissue residence. The specificities and activities of lung T RM are large and likely significant gaps in our understanding of lung defense against respiratory pathogens.…”

Section: Remodeling: Responses To Lung Infection Differ Throughout a mentioning

confidence: 99%

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

Quinton

Mizgerd

2015

Annu. Rev. Physiol.

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Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps.

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“…Other genes expressed by CD8 T RM help avoid being infected and killed by the virus they are trying to control. In the lung, CD8 T RM express the interferon-induced transmembrane protein IFITM3 in order to avoid becoming target of influenza virus infection upon secondary challenge [70]. Of note, CD8 T RM express other interferon-stimulated genes such as ISG20 and IFI44 [69], perhaps to protect themselves from a wide range of viruses.…”

Section: Effector Phase Of Trm Control Of Pathogensmentioning

confidence: 99%

Tissue instruction for migration and retention of TRM cells

Iijima¹,

Iwasaki²

2015

Trends in Immunology

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During infection, a subset of effector T cells seeds the lymphoid and non-lymphoid tissues and gives rise to tissue-resident memory T cells (TRM). Recent findings have provided insight into the molecular and cellular mechanisms underlying tissue instruction of TRM cell homing, as well as the programs involved in their retention and maintenance. We review these findings here, highlighting both common features and distinctions between CD4 TRM and CD8 TRM cells. In this context we examine the role of memory lymphocyte clusters (MLCs), and propose that the MLCs serve as an immediate response center consisting of TRM cells on standby, capable of detecting incoming pathogens and mounting robust local immune responses to contain and limit the spread of infectious agents.

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Enhanced survival of lung tissue-resident memory CD8+ T cells during infection with influenza virus due to selective expression of IFITM3

Cited by 196 publications

References 25 publications

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

The Pulmonary Localization of Virus-Specific T Lymphocytes Is Governed by the Tissue Tropism of Infection

Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

Tissue instruction for migration and retention of TRM cells

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