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.

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

2016 ◽  
Vol 213 (13) ◽  
pp. 3057-3073 ◽  
Author(s):  
Shiki Takamura ◽  
Hideki Yagi ◽  
Yoshiyuki Hakata ◽  
Chihiro Motozono ◽  
Sean R. McMaster ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
De Novo ◽  
Memory T Cells ◽  
Tissue Injury ◽  
Effector Memory ◽  
Respiratory Pathogens ◽  
Damage Site ◽  
Memory Cd8 T Cells ◽  
Specific Localization

CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens.

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

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 Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae following viral pneumonia

2020 ◽  
Author(s):  
Nick P. Goplen ◽  
Yue Wu ◽  
Youngmin Son ◽  
Chaofan Li ◽  
Zheng Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Viral Infections ◽  
Memory T Cells ◽  
Viral Pneumonia ◽  
Lung Pathology ◽  
Tcr Signaling ◽  
Respiratory Viral Infections ◽  
Resident Memory T Cells

AbstractLower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic non-resolving lung pathology and exaggerated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. Strikingly, the depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae following viral pneumonia in aged hosts.

scholarly journals Tissue-resident CD8+ T cells drive age-associated chronic lung sequelae after viral pneumonia

2020 ◽  
Vol 5 (53) ◽  
pp. eabc4557 ◽  
Author(s):  
Nick P. Goplen ◽  
Yue Wu ◽  
Young Min Son ◽  
Chaofan Li ◽  
Zheng Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Viral Infections ◽  
Memory T Cells ◽  
Viral Pneumonia ◽  
Lung Pathology ◽  
Tcr Signaling ◽  
Cell Accumulation ◽  
Resident Memory T Cells

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.

scholarly journals Reduced generation of lung tissue–resident memory T cells during infancy

2017 ◽  
Vol 214 (10) ◽  
pp. 2915-2932 ◽  
Author(s):  
Kyra D. Zens ◽  
Jun Kui Chen ◽  
Rebecca S. Guyer ◽  
Felix L. Wu ◽  
Filip Cvetkovski ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Respiratory Infections ◽  
Influenza Infection ◽  
Life Stage ◽  
Human Infant ◽  
Respiratory Pathogens ◽  
Infant Mouse ◽  
Adult Mice ◽  
Resident Memory T Cells

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant–T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet–regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage.

scholarly journals Superior Protective Immunity against Murine Listeriosis by Combined Vaccination with CpG DNA and Recombinant Salmonella enterica Serovar Typhimurium

2009 ◽  
Vol 77 (12) ◽  
pp. 5501-5508 ◽  
Author(s):  
Christina Berchtold ◽  
Klaus Panthel ◽  
Stefan Jellbauer ◽  
Brigitte Köhn ◽  
Elisabeth Roider ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Salmonella Enterica ◽  
Protective Immunity ◽  
Cd8 T Cell ◽  
Cpg Dna ◽  
Memory Cd8 T Cells ◽  
Type Iii ◽  
Serovar Typhimurium

ABSTRACT Preexisting antivector immunity can severely compromise the ability of Salmonella enterica serovar Typhimurium live vaccines to induce protective CD8 T-cell frequencies after type III secretion system-mediated heterologous protein translocation in orally immunized mice. To circumvent this problem, we injected CpG DNA admixed to the immunodominant p60217-225 peptide from Listeria monocytogenes subcutaneously into BALB/c mice and coadministered a p60-translocating Salmonella strain by the orogastric route. The distribution of tetramer-positive p60217-225-specific effector and memory CD8 T cells was analyzed by costaining of lymphocytes with CD62L and CD127. In contrast to the single oral application of recombinant Salmonella or single immunization with CpG and p60, in the spleens from mice immunized with a combination of both vaccine types a significantly higher level of p60-specific CD8 T cells with a predominance of the effector memory T-cell subset was detected. In vivo protection studies revealed that this CD8 T-cell population conferred sterile protective immunity against a lethal infection with L. monocytogenes. However, p60-specific central memory CD8 T cells induced by single vaccination with CpG and p60 were not able confer effective protection against rapidly replicating intracellular Listeria. In conclusion, we provide compelling evidence that the combination of Salmonella type III-mediated antigen delivery and CpG immunization is an attractive novel vaccination strategy to modulate CD8 differentiation patterns toward distinct antigen-specific T-cell subsets with favorable protective capacities.

scholarly journals Cell Cycle Entry Control in Naïve and Memory CD8+ T Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
David A. Lewis ◽  
Tony Ly
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cytotoxic T Lymphocytes ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Antigen Recognition ◽  
Cellular Growth ◽  
Activated T Cells ◽  
Memory Cd8 T Cells ◽  
Cell Cycle Entry

CD8+ T cells play important roles in immunity and immuno-oncology. Upon antigen recognition and co-stimulation, naïve CD8+ T cells escape from dormancy to engage in a complex programme of cellular growth, cell cycle entry and differentiation, resulting in rapid proliferation cycles that has the net effect of producing clonally expanded, antigen-specific cytotoxic T lymphocytes (CTLs). A fraction of activated T cells will re-enter dormancy by differentiating into memory T cells, which have essential roles in adaptive immunity. In this review, we discuss the current understanding of cell cycle entry control in CD8+ T cells and crosstalk between these mechanisms and pathways regulating immunological phenotypes.

scholarly journals TGF-[beta]-dependent Lymphoid Tissue Residency of Stem-like T cells Limits the Response to Tumor Vaccine

2021 ◽  
Author(s):  
Guo Li ◽  
Liwen Wang ◽  
Chaoyu Ma ◽  
Wei Liao ◽  
Yong Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Tumor Vaccine ◽  
Tumor Control ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Multiple Tumor ◽  
Draining Lymph Node ◽  
Resident Memory T Cells

Stem-like CD8+ T cells represent the key subset responding to multiple tumor immunotherapies, including tumor vaccination. However, the signals that control the differentiation of stem-like T cells are not entirely known. Most previous investigations on stem-like T cells are focused on tumor infiltrating T cells (TIL). The behavior of stem-like T cells in other tissues remains to be elucidated. Tissue-resident memory T cells (TRM) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying TRM features are associated with better tumor control. Here, we found that stem-like CD8+ T cells differentiated into TRMs in a TGF-β and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stem-like T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost TRM features, differentiated into migratory effectors and exerted tumor control.

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