Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles

Pizzolla, Angela; Nguyen, Thi H. O.; Sant, Sneha; Jaffar, Jade; Loudovaris, Thomas; Mannering, Stuart I.; Thomas, Paul G.; Westall, Glen P.; Kedzierska, Katherine; Wakim, Linda M.

doi:10.1172/jci96957

Cited by 157 publications

(189 citation statements)

References 39 publications

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“…Thus, much effort is currently directed toward the concept of universal influenza vaccines. Although CD8 + T cells targeting conserved viral epitopes cannot provide sterilizing immunity to influenza infection, cumulative evidence points toward induction of lung-residing memory CD8 + T cells as a promising strategy to provide heterosubtypic immunity that could broadly limit influenza disease in humans (Kumar et al, 2017; Pizzolla et al, 2018). Our findings suggest that repeated lung immunizations with formulations containing conserved CD8 + T cell target epitopes, might generate durable lung T rm populations capable of sustained heterosubtypic immunity.…”

Section: Discussionmentioning

confidence: 99%

Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity

et al. 2018

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SUMMARY Lung-resident primary memory CD8+ T cell populations (Trm) induced by a single influenza infection decline within months, rendering the host susceptible to new heterosubtypic influenza infections. Here, we demonstrate that, relative to single virus exposure, repeated antigen exposure dramatically alters the dynamics of influenza-specific lung Trm populations. Lung Trm derived from repeatedly stimulated circulating memory CD8+ T cells exhibit extended durability and protective heterosubtypic immunity relative to primary lung Trm. Parabiosis studies reveal that the enhanced durability of lung Trm after multiple antigen encounters resulted from the generation of long-lasting circulating effector memory (Tem) populations, which maintained the ability to be recruited to the lung parenchyma and converted to Trm, in combination with enhanced survival of these cells in the lung. Thus, generating a long-lasting Trm precursor pool through repeated intranasal immunizations might be a promising strategy to establish long-lasting lung Trm-mediated heterosubtypic immunity against influenza.

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Section: Discussionmentioning

confidence: 99%

Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity

et al. 2018

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“…63–66 Further, it has been recently confirmed that influenza-specific T RM cells isolated from human lungs mount a robust proliferative response with superior effector functions. 67 …”

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 99%

“…67,72,73 Further, TCR signal can induce the expression of anti-viral protein IFITM3 (Interferon Induced Transmembrane Protein 3) in lung T RM cells. IFITM3 protects lung T RM cells from direct viral infection-induced cell death.…”

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 99%

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Tissue-Specific Control of Tissue-Resident Memory T Cells

Liu

Zhang

2018

Crit Rev Immunol

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Tissue-resident memory T (TRM) cells have emerged to be a major component of T cell biology. Recent investigations have greatly advanced our understanding of TRMs. Common features have been discovered to distinguish memory T cells residing in various mucosal and non-mucosal tissues from their circulating counterparts. Given that most organs and tissues contain unique microenvironment, local signal-induced tissue-specific features are tightly associated with the differentiation, homeostasis and protective functions of TRMs. We will discuss the recent advances in TRM field with a special emphasis on the interaction between local signals and TRM cells in the context of individual tissue environment.

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“…Tissue-resident memory T cells (T rm ) are compartmentalized away from the circulating pool via the expression of the tissue-retention signals CD69 and/or CD103 [58]. They can be directed against viruses that invade these sites: for example, HBV-specific CD8 + T rm have been found in the human liver [59], murine herpes simplex virus 1-specific T rm in the lamina propria of the vagina [60] and human influenza A-specific T cells in the lung [61]. CD8 + T rm provide rapid antigen-specific recall responses in situ and therefore act as highly functional defence specialists, with adaptations imposed by their local niche.…”

Section: Tissue Residencymentioning

confidence: 99%

T cell metabolism in chronic viral infection

Pallett

Schmidt

Schurich

2019

Clinical and Experimental Immunology

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T cells are a fundamental component of the adaptive immune response in the context of both acute and chronic viral infection. Tight control over the metabolic processes within T cells provides an additional level of immune regulation that is interlinked with nutrient sensing and the continued balancing of co-stimulatory and co-inhibitory signals. Underpinning T cell responsiveness for viral control are a number of phenotypic and functional adaptations ensuring adequate nutrient uptake and their utilization. T cells responding to persistent viral infections often exhibit a profile associated with immune cell exhaustion and a dysregulated metabolic profile, driven by a combination of chronic antigenic stimulation and signals from the local microenvironment. Understanding alterations in these metabolic processes provides an important basis for immunotherapeutic strategies to treat persistent infections. T cell metabolism in chronic viral infection OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIESTranslating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experimental Immunology 2019, 197: 141-142. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity. Clinical and Experimental Immunology 2019, 197: 161-169. Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis.

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Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles

Cited by 157 publications

References 39 publications

Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity

Repeated Antigen Exposure Extends the Durability of Influenza-Specific Lung-Resident Memory CD8+ T Cells and Heterosubtypic Immunity

Tissue-Specific Control of Tissue-Resident Memory T Cells

T cell metabolism in chronic viral infection

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