scholarly journals Antigen-dependent competition shapes the local repertoire of tissue-resident memory CD8+ T cells

2016 ◽  
Vol 213 (13) ◽  
pp. 3075-3086 ◽  
Author(s):  
Andreas Muschaweckh ◽  
Veit R. Buchholz ◽  
Anne Fellenzer ◽  
Christian Hessel ◽  
Paul-Albert König ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Fate ◽  
Cd8 T Cells ◽  
Immune Surveillance ◽  
Cell Formation ◽  
Memory Cd8 T Cells ◽  
Tcr Signals ◽  
Necessary And Sufficient ◽  
Resident Memory T Cells ◽  
Cross Competition

Tissue-resident memory CD8+ T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector. We found that CD8+ T cells of different specificities underwent antigen-dependent competition in the infected tissue, which shaped the composition of the local pool of TRM cells. This local cross-competition was active for T cells recognizing antigens that are coexpressed by infected cells. In contrast, TRM cell development remained largely undisturbed by the presence of potential competitors when antigens expressed in the same tissue were segregated through infection with antigenically distinct viral quasispecies. Functionally, local cross-competition might serve as a gatekeeping mechanism to regulate access to the resident memory niche and to fine-tune the local repertoire of antiviral TRM cells.

scholarly journals CXCR6 regulates localization of tissue-resident memory CD8 T cells to the airways

2019 ◽  
Vol 216 (12) ◽  
pp. 2748-2762 ◽  
Author(s):  
Alexander N. Wein ◽  
Sean R. McMaster ◽  
Shiki Takamura ◽  
Paul R. Dunbar ◽  
Emily K. Cartwright ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Memory T Cells ◽  
Respiratory Pathogens ◽  
First Line ◽  
Memory Cd8 T Cells ◽  
Effector Functions ◽  
Signaling Axis ◽  
Resident Memory T Cells

Resident memory T cells (TRM cells) are an important first-line defense against respiratory pathogens, but the unique contributions of lung TRM cell populations to protective immunity and the factors that govern their localization to different compartments of the lung are not well understood. Here, we show that airway and interstitial TRM cells have distinct effector functions and that CXCR6 controls the partitioning of TRM cells within the lung by recruiting CD8 TRM cells to the airways. The absence of CXCR6 significantly decreases airway CD8 TRM cells due to altered trafficking of CXCR6−/− cells within the lung, and not decreased survival in the airways. CXCL16, the ligand for CXCR6, is localized primarily at the respiratory epithelium, and mice lacking CXCL16 also had decreased CD8 TRM cells in the airways. Finally, blocking CXCL16 inhibited the steady-state maintenance of airway TRM cells. Thus, the CXCR6/CXCL16 signaling axis controls the localization of TRM cells to different compartments of the lung and maintains airway TRM cells.

Circulating memory CD8 + T cells are limited in forming CD103 + tissue‐resident memory T cells at mucosal sites after reinfection

2020 ◽  
Author(s):  
Felix M. Behr ◽  
Ammarina Beumer‐Chuwonpad ◽  
Natasja A. M. Kragten ◽  
Thomas H. Wesselink ◽  
Regina Stark ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Memory Cd8 T Cells ◽  
Resident Memory T Cells

scholarly journals Ptpn2 and KLRG1 regulate the generation and function of tissue-resident memory CD8+ T cells in skin

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Katharina Hochheiser ◽  
Florian Wiede ◽  
Teagan Wagner ◽  
David Freestone ◽  
Matthias H. Enders ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cell Formation ◽  
Cell Receptor ◽  
Cytokine Signaling ◽  
Memory Cd8 T Cells ◽  
Simplex Virus ◽  
And Function ◽  
Hsv 1

Tissue-resident memory T cells (TRM cells) are key elements of tissue immunity. Here, we investigated the role of the regulator of T cell receptor and cytokine signaling, Ptpn2, in the formation and function of TRM cells in skin. Ptpn2-deficient CD8+ T cells displayed a marked defect in generating CD69+ CD103+ TRM cells in response to herpes simplex virus type 1 (HSV-1) skin infection. This was accompanied by a reduction in the proportion of KLRG1− memory precursor cells and a transcriptional bias toward terminal differentiation. Of note, forced expression of KLRG1 was sufficient to impede TRM cell formation. Normalizing memory precursor frequencies by transferring equal numbers of KLRG1− cells restored TRM generation, demonstrating that Ptpn2 impacted skin seeding with precursors rather than downstream TRM cell differentiation. Importantly, Ptpn2-deficient TRM cells augmented skin autoimmunity but also afforded superior protection from HSV-1 infection. Our results emphasize that KLRG1 repression is required for optimal TRM cell formation in skin and reveal an important role of Ptpn2 in regulating TRM cell functionality.

Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert

Science ◽  
2014 ◽  
Vol 346 (6205) ◽  
pp. 101-105 ◽  
Author(s):  
Silvia Ariotti ◽  
Marc A. Hogenbirk ◽  
Feline E. Dijkgraaf ◽  
Lindy L. Visser ◽  
Mirjam E. Hoekstra ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Mouse Skin ◽  
Memory Cd8 T Cells ◽  
Vaccination Strategies ◽  
Rapid Control ◽  
Pathogen Entry ◽  
Specific Tissue ◽  
Resident Memory T Cells

After an infection, pathogen-specific tissue-resident memory T cells (TRM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create TRM cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how TRM cells provide such pathogen protection. Here, we demonstrate that activated TRM cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This “pathogen alert” allows skin TRM cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8+ T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.

scholarly journals Viral MHCI inhibition evades tissue-resident memory T cell formation and responses

2018 ◽  
Vol 216 (1) ◽  
pp. 117-132 ◽  
Author(s):  
Elvin J. Lauron ◽  
Liping Yang ◽  
Ian B. Harvey ◽  
Dorothy K. Sojka ◽  
Graham D. Williams ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Cell Formation ◽  
Memory Cd8 T Cells ◽  
Effector Functions ◽  
Cross Presentation ◽  
Cognate Antigen

Tissue-resident memory CD8+ T cells (TRMs) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8+ T cells, suggesting that these mechanisms may also apply to TRM-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of TRMs is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4+ and CD8+ TRMs, but its effects on the local microenvironment compensate to promote antigen-specific CD8+ TRM formation. Unexpectedly, local cognate antigen enhances CD8+ TRM development even in the context of viral MHCI inhibition and CD8+ T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven TRM differentiation. However, local cognate antigen is not required for CD8+ TRM maintenance. We also show that viral MHCI inhibition efficiently evades CD8+ TRM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral TRMs.

scholarly journals Chemokine receptor CXCR3 facilitates CD8+ T cell differentiation into short-lived effector cells leading to memory degeneration

2011 ◽  
Vol 208 (8) ◽  
pp. 1605-1620 ◽  
Author(s):  
Makoto Kurachi ◽  
Junko Kurachi ◽  
Fumiko Suenaga ◽  
Tatsuya Tsukui ◽  
Jun Abe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Fate ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Memory Cd8 T Cells ◽  
Effector Cells ◽  
Inflammatory Stimuli ◽  
Cell Commitment

Strength of inflammatory stimuli during the early expansion phase plays a crucial role in the effector versus memory cell fate decision of CD8+ T cells. But it is not known how early lymphocyte distribution after infection has an impact on this process. We demonstrate that the chemokine receptor CXCR3 is involved in promoting CD8+ T cell commitment to an effector fate rather than a memory fate by regulating T cell recruitment to an antigen/inflammation site. After systemic viral or bacterial infection, the contraction of CXCR3−/− antigen-specific CD8+ T cells is significantly attenuated, resulting in massive accumulation of fully functional memory CD8+ T cells. Early after infection, CXCR3−/− antigen-specific CD8+ T cells fail to cluster at the marginal zone in the spleen where inflammatory cytokines such as IL-12 and IFN-α are abundant, thus receiving relatively weak inflammatory stimuli. Consequently, CXCR3−/− CD8+ T cells exhibit transient expression of CD25 and preferentially differentiate into memory precursor effector cells as compared with wild-type CD8+ T cells. This series of events has important implications for development of vaccination strategies to generate increased numbers of antigen-specific memory CD8+ T cells via inhibition of CXCR3-mediated T cell migration to inflamed microenvironments.

scholarly journals Selected MicroRNAs Define Cell Fate Determination of Murine Central Memory CD8 T Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e11243 ◽  
Author(s):  
Gonzalo Almanza ◽  
Antonio Fernandez ◽  
Stefano Volinia ◽  
Xochitl Cortez-Gonzalez ◽  
Carlo M. Croce ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Fate ◽  
Cd8 T Cells ◽  
Central Memory ◽  
Cell Fate Determination ◽  
Memory Cd8 T Cells ◽  
Fate Determination

scholarly journals Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment

2021 ◽  
Author(s):  
Athanasios Papadas ◽  
Gauri Deb ◽  
Adam Officer ◽  
Alexander Cicala ◽  
Chelsea Hope ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cell Fate ◽  
Cd8 T Cells ◽  
Tumor Stroma ◽  
Lymphoid Cells ◽  
Adult Tissue ◽  
Tumor Seeding ◽  
Embryonic Morphogenesis ◽  
Necessary And Sufficient

Stimulatory dendritic cells (SDC), enriched within Batf3-DC (cDC1), engage in productive interactions with CD8+ effectors along tumor-stroma boundaries. The paradoxical accumulation of poised cross-presenting Batf3-DC within stromal sheets, distal to tumoral nests, is unlikely to simply reflect passive exclusion away from immunosuppressive tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling may generate developmentally conserved cell-fate cues that regulate Batf3-DC behavior. We find that CD8+ T-cells massively infiltrate tumor matrices undergoing proteoglycan versican (VCAN) proteolysis, an essential organ-sculpting modification in development and adult tissue-plane forging. VCAN proteolysis releases a bioactive fragment (matrikine), versikine, that is necessary and sufficient for Batf3-DC accumulation. Versikine does not influence tumor-seeding pre-DC differentiation; rather, it orchestrates a distinctive activation program conferring exquisite sensitivity to DNA-sensing, coupled with survival support from atypical innate lymphoid cells. Thus, homeostatic signals from stroma invasion regulate SDC survival and activity to promote T-cell inflammation.

scholarly journals Strong homeostatic TCR signals induce formation of self‐tolerant virtual memory CD8 T cells

2018 ◽  
Vol 37 (14) ◽  
Author(s):  
Ales Drobek ◽  
Alena Moudra ◽  
Daniel Mueller ◽  
Martina Huranova ◽  
Veronika Horkova ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Virtual Memory ◽  
Memory Cd8 T Cells ◽  
Tcr Signals
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