Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

Takamura, Shiki; Yagi, Hideki; Hakata, Yoshiyuki; Motozono, Chihiro; McMaster, Sean R.; Masumoto, Tomoko; Fujisawa, Makoto; Chikaishi, Tomomi; Komeda, Junko; Itoh, Jun; Umemura, Miki; Kyusai, Ami; Tomura, Michio; Nakayama, Toshinori; Woodland, David L.; Kohlmeier, Jacob E.; Miyazawa, Masaaki

doi:10.1084/jem.20160938

Cited by 191 publications

(330 citation statements)

References 62 publications

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“…In contrast to antigen-independent and local inflammation-driven T RM differentiation in the vagina and salivary gland, local cognate antigen is essential for lung T RM differentiation, 47,64 consistent with the findings that T cells with different TCR specificity elicit distinct T RM forming potential during polyclonal response against influenza virus infection in mice. 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.…”

Section: Tissue Specific Features Of Trm Cellssupporting

confidence: 85%

“…However, CD69 deficient T cells can differentiate into CD103 + T RM s in the skin, similar as the situation in lung T RM cells. 47 These results demonstrate that CD69 per se is not required for the subsequent differentiation of T RM cells. The induction of CD69 in skin T RM cells is independent of TGF-β and type I interferon (IFN).…”

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 79%

“…These lung T RM niches are the tissue repair-associated regions and co-localize with the production of T RM promoting factors TGF-β and IL-15. 47,72 Notably, the regeneration of damaged airway epithelium is also TGF-β-dependent, 78 providing an example of complex functions of TGF-β signaling in both local immunity and tissue homeostasis. The gradual decline of lung T RM cells is caused by the completion of injured lung regeneration and the shrinking of lung T RM niches.…”

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 99%

“…Considering that T EM cells continuously migrate and differentiate into lung T RM cell after influenza viral infection, 75 it seems counterintuitive that seven weeks of parabiosis does not lead to significant de novo lung T RM formation in a similar animal model. 47 One possible explanation may be that parabiosis surgery itself causes unexpected inflammation and tissue damage. Systemic and local inflammatory signals introduced by surgical procedures may alter the migration of circulating memory T cells as TCM cells are sensitive to inflammation-induced O-glycosylation and migration.…”

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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Section: Tissue Specific Features Of Trm Cellssupporting

confidence: 85%

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 79%

Section: Tissue Specific Features Of Trm Cellsmentioning

confidence: 99%

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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“…T‐cells that encounter their antigen at the infection site are likely to receive tissue‐specific cues that influence their function and memory potential. The presentation of specific antigen at the infected tissue is required for the formation of CD4 Trm cells, but may not be necessary for CD8 Trm cells 31, 46, 47, 48. These data indicate that vaccines aimed at generating protective Trm CD4 T‐cells must drive antigen presentation within the tissue targeted by the pathogen.…”

Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 99%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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SummaryImmunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T‐cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T‐cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T‐cells play many different roles during the immune response coordinating the actions of many other cells. In order to harness the diverse protective effects of memory CD4 T‐cells, we need to understand how memory CD4 T‐cells are generated and how they protect the host. Here we review recent findings on the location of different subsets of memory CD4 T‐cells that are found in peripheral tissues (tissue resident memory T‐cells) and in the circulation (central and effector memory T‐cells). We discuss the generation of these cells, and the evidence that demonstrates how they provide immune protection in animal and human challenge models.

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Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

Dong

Wang

2021

Advanced NanoBiomed Research

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Influenza is one of the most severe and contagious respiratory infectious diseases. Influenza virus infection causes annual epidemics and occasional pandemics, resulting in an enormous health and economic burden worldwide. During the 2019-2020 flu season, the centers for disease control and prevention (CDC) estimates that flu caused 38 million illnesses, including 18 million medical visits, 405 000 hospitalizations, and 22 000 deaths in the United States. [1] Influenza viruses are enveloped RNA viruses of the Orthomyxoviridae family. Because the RNA polymerases lack the proofreading function, influenza viruses undergo constant antigenic drift and shift within animal and human reservoirs. [2] Influenza A viruses (IAVs) and influenza B viruses (IBVs) are the main circulating viruses that affect human health. So far, 18 hemagglutinin (HA) subtypes belonging to two HA phylogenetic groups and 11 neuraminidase (NA) subtypes have been identified for IAVs. [3] The IAVs H1N1 and H3N2 currently cause most epidemic diseases in humans. IBVs form a single antigenic group with two distinct lineages: Victoria and Yamagata.Seasonal vaccination is the most cost-effective method to combat influenza infection. However, current seasonal flu vaccines induce strain-specific immunity that rapidly wanes and displays low efficiencies against mismatched circulating strains and no effect on pandemics. The vaccines need annual reformulation based on the prediction by the WHO Global Influenza Surveillance and Response System to counter antigenic variations. [4] This uncertainty makes mismatches occur, resulting in suboptimal immunity. Fewer influenza cases occurred in the past 2020-2021 flu season in the United States than in any on record, [5] probably due to the widespread use of face masks and social distance to control COVID-19. The lack of exposure to the flu may make the population more susceptible to the virus when it returns. [6] Parallelly, predicting which strains will be circulating in the upcoming flu season and selecting vaccine manufacturing will be more challenging than ever.A next-generation universal influenza vaccine that elicits long-lasting cross-protective immunity against variant influenza strains will overcome the limitations of the current flu v accines. [7,8] Nanotechnology plays an indispensable role in the development of such vaccines. [9][10][11] Influenza viruses are nanosized particles enveloped by lipid membranes inserted with surface glycoprotein spikes. Nanoparticle vaccines can optimally mimic the influenza virus nanostructure with high antigen loads, facilitate targeted delivery and controlled antigen release, and synergize with molecular adjuvants to improve vaccine potency and breadth. Moreover, nanoparticle vaccines can facilitate rapid and scalable production, minimize cold-chain dependence, incorporate antigens in a flexibly modular fashion, and be affordably produced. Up to date, a variety of nanoparticle formulations have shown promising results in generating cross-reactive influenza immunity.

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Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

Abstract: Takamura et al. show that most lung CD8+ TRM cells are not maintained in the inducible bronchus-associated lymphoid tissue (iBALT) but are maintained in specific niches created at the site of tissue regeneration, which are termed as repair-associated memory depots (RAMDs).

Cited by 191 publications

References 62 publications

Tissue-Specific Control of Tissue-Resident Memory T Cells

Tissue-Specific Control of Tissue-Resident Memory T Cells

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats

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