The α1β1 Integrin and TNF Receptor II Protect Airway CD8+ Effector T Cells from Apoptosis during Influenza Infection

Richter, Martin; Topham, David J.

doi:10.4049/jimmunol.179.8.5054

Cited by 59 publications

(58 citation statements)

References 51 publications

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“…Ccr2 , Ccr5 , Itga1 , Itgb1 , Gpr183 , Rgs16 ), with some having an essential role in the recruitment of CD8 T cells in the lung following infection by a pathogen. Indeed, the chemokine receptor CCR5 has been shown to be necessary for the recruitment of peripheral memory CD8 T cells to the lung24 and the Itga1 / Itgb1 genes code for VLA1, an integrin involved in the retention25 and survival26 of CD8 memory cells in the lung. To validate if this differential expression could correlate with different migration patterns following a virus induced stimulation, we transferred equivalent numbers of naive, TIM or Flu-TM F5 CD8 cells in naive C57BL/6 J hosts that were subsequently infected intra-nasally with an infectious dose of influenza.…”

Section: Resultsmentioning

confidence: 99%

“…However we cannot exclude that other differentially expressed HP1 gene, coding for proteins such as chemokine receptors regulators ( Rgs16 ), actin cytoskeleton regulators ( Anxa1 , Rhoq , Yes1 ) are also involved in the control of memory CD8 T cells extravasation and tissue migration. Furthermore, both VLA1 and CCR5 could also contribute to the increased survival of CD8 T cells within the lung2641. They might not be the only factors favouring the survival of Flu-TM as the HP1 signature also includes genes that code for proteins that will increase their resistance to environmental stress or to pathogen infection.…”

Section: Discussionmentioning

confidence: 99%

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Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune signatures of protective spleen memory CD8 T cells

Brinza

Djebali

Tomkowiak

et al. 2016

Sci Rep

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“…2H). Thus, influenza infection in mice increases TNFR2 is expressed on and shed by influenza-specific effector CD8 + T cells As it has been reported that memTNFR2 is expressed on influenza-specific CD8 + T cells in the lungs of infected mice [4,34], we examined whether CD8 + T cells contributed to the increase in solTNFR2 levels following influenza infection in mice. CD8 + T cells were detectable in the airways as early as day 5 postinfection and peaked in absolute numbers between days 7 and 10 ( Fig.…”

Section: Soltnfr2 Production Is Increased After Influenza Infection Imentioning

confidence: 98%

“…TNFR2 mediates these effects by binding to mem-or solTNF-a [2][3][4]. TNFR2 is expressed on the surface following activation of naive CD8 + T cells, where it can function as a costimulatory molecule, lowering the threshold for activation and enhancing proliferation [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection

DeBerge

Ely

Wright

et al. 2015

Journal of Leukocyte Biology

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Elevated levels of solTNFR2 are observed in a variety of human pathophysiological conditions but regulation of TNFR2 levels during disease is not well understood. We found that solTNFR2 levels were increased following influenza infection or live-attenuated influenza virus challenge in mice and humans, respectively. As influenza-specific CD8(+) T cells up-regulated expression of TNFR2 after infection in mice, we hypothesized that CD8(+) T cells contributed, in part, to solTNFR2 production after influenza infection and were interested in the mechanisms by which CD8(+) T cells regulate TNFR2 shedding. Activation of these cells by TCR stimulation resulted in enhanced shedding of TNFR2 that required actin remodeling and lipid raft formation and was dependent on MAPK/ERK signaling. Furthermore, we identified ADAM17 as the protease responsible for TNFR2 shedding by CD8(+) T cells, with ADAM17 and TNFR2 required in "cis" for shedding to occur. We observed similar activation thresholds for TNF-α expression and TNFR2 shedding, suggesting that solTNFR2 functioned, in part, to regulate solTNF-α levels. Production of solTNFR2 by activated CD8(+) T cells reduced the availability of solTNF-α released by these cells, and TNFR2 blockade during influenza infection in mice enhanced the levels of solTNF-α, supporting this hypothesis. Taken together, this study identifies critical cellular mechanisms regulating TNFR2 shedding on CD8(+) T cells and demonstrates that TNFR2 contributes, in part, to the regulation of TNF-α levels during infection.

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“…As a result, the different subsets localize to different areas within the lungs: CD8+ T cells that preferentially express α 1 β 1 locate near the basement membranes of either the airways or blood vessels, whereas α 2 β 1 CD4+ T cells primarily localize within the interstitial spaces. After influenza virus infection, α 1 β 1 -binding of collagen allows memory T cells to persist and function in the lungs (59, 113, 114). Similarly, signaling via CD44 is necessary for the survival of Th1 effector cells in lungs and the transition to memory (115).…”

Section: Role Of Location and Mr Signaling On The Effector To Memory mentioning

confidence: 99%

Location, Location, Location: The Impact of Migratory Heterogeneity on T Cell Function

Baaten¹,

Cooper²,

Swain³

et al. 2013

Front. Immunol.

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T cell migration is crucial for an effective adaptive immune response to invading pathogens. Naive and memory T cells encounter pathogen antigens, become activated, and differentiate into effector cells in secondary lymphoid tissues, and then migrate to the site(s) of infection where they exert effector activities that control and eliminate pathogens. To achieve activation, efficient effector function, and good memory formation, T cells must traffic between lymphoid and non-lymphoid tissues within the body. This complex process is facilitated by chemokine receptors, selectins, CD44, and integrins that mediate the interactions of T cells with the environment. The expression patterns of these migration receptors (MR) dictate the tissues into which the effector T cells migrate and enable them to occupy specific niches within the tissue. While MR have been considered primarily to facilitate cell movement, we highlight how the heterogeneity of signaling through these receptors influences the function and fate of T cells in situ. We explore what drives MR expression heterogeneity, how this affects migration, and how this impacts T cell effector function and memory formation.

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The α1β1 Integrin and TNF Receptor II Protect Airway CD8+ Effector T Cells from Apoptosis during Influenza Infection

Cited by 59 publications

References 51 publications

Immune signatures of protective spleen memory CD8 T cells

Immune signatures of protective spleen memory CD8 T cells

Shedding of TNF receptor 2 by effector CD8+ T cells by ADAM17 is important for regulating TNF-α availability during influenza infection

Location, Location, Location: The Impact of Migratory Heterogeneity on T Cell Function

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