GITRL on inflammatory antigen presenting cells in the lung parenchyma provides signal 4 for T-cell accumulation and tissue-resident memory T-cell formation

Chu, Kuan‐Lun; Batista, Nathália Vieira; Wang, Kuan Chung; Zhou, Angela; Watts, Tania H.

doi:10.1038/s41385-018-0105-5

Cited by 19 publications

(31 citation statements)

References 47 publications

(75 reference statements)

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“…42 We have shown that GITR is required for the optimal formation of lung CD4 + and CD8 + Trm after influenza infection. 8 Here, using mixed bone marrow chimeras, we show that GITR regulates CXCR6 expression in both CD4 + and CD8 + T cells after influenza infection. It remains to be determined if the small increase in CXCR6 expression induced by GITR signaling contributes to the effect GITR +/+ and GITR −/− OT-I cells were evaluated in Ly6C hi CX3CR1 hi , Ly6C hi CX3CR1 lo , or Ly6C lo CX3CR1 lo compartments in the lung.…”

Section: F I G U R Ementioning

confidence: 77%

“…GITR is required for maximal formation of lung CD8 + Trm following influenza virus infection. 8 As CXCR6 has been implicated in CD8 + Trm formation in the skin and lung airway, 41,42 we used GITR +/+ : GITR −/mixed bone marrow chimeras to ask whether GITR also regulates CXCR6 expression in CD8 + T cells during influenza infection ( Fig. 9A).…”

Section: Gitr Regulates Cxcr6 Expression In Ly6c Hi Cx3cr1 Lo and Ly6mentioning

confidence: 99%

“…In the case of CD8 + T cells, we observed the greatest effect of GITR on accumulation and CXCR6 expression on the least differentiated effector T cells, consistent with an important role for GITR in Trm formation. 8 Thus, GITR plays a crucial role in sustaining both highly differentiated effector cells as well as precursors of Trm, with differential effects on effector subpopulations.…”

Section: F I G U R Ementioning

confidence: 99%

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GITR differentially affects lung effector T cell subpopulations during influenza virus infection

Chu

Batista

Girard

et al. 2020

Journal of Leukocyte Biology

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Tissue resident memory T cells (Trm) are critical for local protection against reinfection. The accumulation of T cells in the tissues requires a post‐priming signal from TNFR superfamily members, referred to as signal 4. Glucocorticoid‐induced TNFR‐related protein (GITR; TNFRSF18) signaling is important for this post‐priming signal and for Trm formation during respiratory infection with influenza virus. As GITR signaling impacts both effector T cell accumulation and Trm formation, we asked if GITR differentially affects subsets of effector cells with different memory potential. Effector CD4+ T cells can be subdivided into 2 populations based on expression of lymphocyte antigen 6C (Ly6C), whereas effector CD8+ cells can be divided into 3 populations based on Ly6C and CX3CR1. The Ly6Chi and CX3CR1hi T cell populations represent the most differentiated effector T cells. Upon transfer, the Ly6Clo CD4+ effector T cells preferentially enter the lung parenchyma, compared to the Ly6Chi CD4+ T cells. We show that GITR had a similar effect on the accumulation of both the Ly6Chi and Ly6Clo CD4+ T cell subsets. In contrast, whereas GITR increased the accumulation of all three CD8+ T cell subsets defined by CX3CR1 and Ly6C expression, it had a more substantial effect on the least differentiated Ly6Clo CX3CR1lo subset. Moreover, GITR selectively up‐regulated CXCR6 on the less differentiated CX3CR1lo CD8+ T cell subsets and induced a small but significant increase in CD127 selectively on the Ly6Clo CD4+ T cell subset. Thus, GITR contributes to accumulation of both differentiated effector cells as well as memory precursors, but with some differences between subsets.

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Section: F I G U R Ementioning

confidence: 77%

Section: Gitr Regulates Cxcr6 Expression In Ly6c Hi Cx3cr1 Lo and Ly6mentioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

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GITR differentially affects lung effector T cell subpopulations during influenza virus infection

Chu

Batista

Girard

et al. 2020

Journal of Leukocyte Biology

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“…Given the unique ability of CD103 + respiratory DC to provide strong stimulatory signals in the draining LN, thereby generating effector CD8 + T cells that preferentially home back to the lung (55), local reactivation by respiratory DC may promote terminal effector maturation rather than memory differentiation (56–58). Thus, other APC subsets, such as pulmonary macrophages, that accumulate in the RAMD during the early phase of infection may be necessary to provide the optimal antigen signaling required for T RM development (59, 60).…”

Section: Generation and Maintenance Of Canonical Trm Cells In The Lungmentioning

confidence: 99%

Establishment and Maintenance of Conventional and Circulation-Driven Lung-Resident Memory CD8+ T Cells Following Respiratory Virus Infections

Takamura

Kohlmeier

2019

Front. Immunol.

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Antigen-specific CD8 + tissue-resident memory T cells (T RM cells) persist in the lung following resolution of a respiratory virus infection and provide first-line defense against reinfection. In contrast to other memory T cell populations, such as central memory T cells that circulate between lymph and blood, and effector memory T cells (T EM cells) that circulate between blood and peripheral tissues, T RM cells are best defined by their permanent residency in the tissues and their independence from circulatory T cell populations. Consistent with this, we recently demonstrated that CD8 + T RM cells primarily reside within specific niches in the lung (Repair-Associated Memory Depots; RAMD) that normally exclude CD8 + T EM cells. However, it has also been reported that circulating CD8 + T EM cells continuously convert into CD8 + T RM cells in the lung interstitium, helping to sustain T RM numbers. The relative contributions of these two mechanisms of CD8 + T RM cells maintenance in the lung has been the source of vigorous debate. Here we propose a model in which the majority of CD8 + T RM cells are maintained within RAMD (conventional T RM ) whereas a small fraction of T RM are derived from circulating CD8 + T EM cells and maintained in the interstitium. The numbers of both types of T RM cells wane over time due to declines in both RAMD availability and the overall number of T EM in the circulation. This model is consistent with most published reports and has important implications for the development of vaccines designed to elicit protective T cell memory in the lung.

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“…As knowledge is gained in these issues, we will have more of the needed insight into the most critical deficiencies in the influenza-specific CD4 T-cell repertoire and, with this, the needed framework for improved vaccine strategies. Studies in both animal models and more recent studies in humans have provided evidence that influenzaspecific T cells can establish long-term tissue resident memory (Zens et al 2016(Zens et al , 2017Oja et al 2018;Chu et al 2019;Snyder et al 2019) that may provide protective immunity very early after infection.…”

Section: Abundance and Specificity Of Human Influenza-specific Cd4 T mentioning

confidence: 99%

Immunity to Influenza Infection in Humans

Topham

DeDiego

Nogales

et al. 2019

Cold Spring Harb Perspect Med

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This review discusses the human immune responses to influenza infection with some insights from studies using animal models, such as experimental infection of mice. Recent technological advances in the study of human immune responses have greatly added to our knowledge of the infection and immune responses, and therefore much of the focus is on recent studies that have moved the field forward. We consider the complexity of the adaptive response generated by many sequential encounters through infection and vaccination.

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GITRL on inflammatory antigen presenting cells in the lung parenchyma provides signal 4 for T-cell accumulation and tissue-resident memory T-cell formation

Cited by 19 publications

References 47 publications

GITR differentially affects lung effector T cell subpopulations during influenza virus infection

GITR differentially affects lung effector T cell subpopulations during influenza virus infection

Establishment and Maintenance of Conventional and Circulation-Driven Lung-Resident Memory CD8+ T Cells Following Respiratory Virus Infections

Immunity to Influenza Infection in Humans

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