scholarly journals Human intestinal tissue-resident memory CD8+ T cells comprise transcriptionally and functionally distinct subsets

2019 ◽  
Author(s):  
Michael E.B. FitzPatrick ◽  
Nicholas M. Provine ◽  
Lucy C. Garner ◽  
Kate Powell ◽  
Ali Amini ◽  
...  
Keyword(s):  
T Cells ◽  
Transcriptional Profiling ◽  
Transplant Recipients ◽  
Functional Heterogeneity ◽  
Memory Cd8 T Cells ◽  
Transcriptional Signature ◽  
Β2 Integrin ◽  
Intestinal Lymphocytes ◽  
Cytotoxic Molecules ◽  
Intestinal Transplant

AbstractTissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined, and definitive markers of CD103-TRM cells are lacking. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through the study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified four conventional TRM populations, with two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating the two CD8+ populations, including differential expression of key residency-associated genes and cytotoxic molecules. Flow cytometry of recipient-derived cells infiltrating the graft and intestinal lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes, with β2-integrin acting as a CD103-CD8+ TRM marker. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103-TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal TRM cells, and suggest a role for β2-integrin in TRM development.SummaryHeterogeneity within human tissue-resident memory T (TRM) cells is poorly understood. We show that transcriptionally, phenotypically, and functionally distinct CD4+ and CD8+ TRM subsets exist in the human intestine, and that β2-integrin expression identifies a distinct population of CD8+ TRM cells.

scholarly journals Tissue-Resident-Memory CD8+ T Cells Bridge Innate Immune Responses in Neighboring Epithelial Cells to Control Human Genital Herpes

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Peng ◽  
Khamsone Phasouk ◽  
Catherine N. Sodroski ◽  
Sijie Sun ◽  
Yon Hwangbo ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Early Stage ◽  
Transcriptional Profiling ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Normal Human Skin ◽  
Memory Cd8 T Cells ◽  
Simplex Virus ◽  
The Impact

Tissue-resident-memory T cells (TRM) populate the body’s barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser capture microdissection and transcriptional profiling, we investigate the impact of CD8TRM on the tissue microenvironment in skin biopsies sequentially obtained from a clinical cohort of diverse disease expression during herpes simplex virus 2 (HSV-2) reactivation. Epithelial cells neighboring CD8TRM display elevated and widespread innate and cell-intrinsic antiviral signature expression, largely related to IFNG expression. Detailed evaluation via T-cell receptor reconstruction confirms that CD8TRM recognize viral-infected cells at the specific HSV-2 peptide/HLA level. The hierarchical pattern of core IFN-γ signature expression is well-conserved in normal human skin across various anatomic sites, while elevation of IFI16, TRIM 22, IFITM2, IFITM3, MX1, MX2, STAT1, IRF7, ISG15, IFI44, CXCL10 and CCL5 expression is associated with HSV-2-affected asymptomatic tissue. In primary human cells, IFN-γ pretreatment reduces gene transcription at the immediate-early stage of virus lifecycle, enhances IFI16 restriction of wild-type HSV-2 replication and renders favorable kinetics for host protection. Thus, the adaptive immune response through antigen-specific recognition instructs innate and cell-intrinsic antiviral machinery to control herpes reactivation, a reversal of the canonical thinking of innate activating adaptive immunity in primary infection. Communication from CD8TRM to surrounding epithelial cells to activate broad innate resistance might be critical in restraining various viral diseases.

scholarly journals Allograft Rejection by Primed/Memory CD8+T Cells Is CD154 Blockade Resistant: Therapeutic Implications for Sensitized Transplant Recipients

2002 ◽  
Vol 169 (8) ◽  
pp. 4667-4673 ◽  
Author(s):  
Yuan Zhai ◽  
Lingzhong Meng ◽  
Feng Gao ◽  
Ronald W. Busuttil ◽  
Jerzy W. Kupiec-Weglinski
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Allograft Rejection ◽  
Transplant Recipients ◽  
Memory Cd8 T Cells ◽  
Therapeutic Implications

scholarly journals Comparative analysis reveals a role for TGF-β in shaping the residency-related transcriptional signature in tissue-resident memory CD8+ T cells

PLoS ONE ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. e0210495 ◽  
Author(s):  
Artika P. Nath ◽  
Asolina Braun ◽  
Scott C. Ritchie ◽  
Francis R. Carbone ◽  
Laura K. Mackay ◽  
...  
Keyword(s):  
T Cells ◽  
Comparative Analysis ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Transcriptional Signature

scholarly journals CD8+ T cell signature in acute SARS-CoV-2 infection identifies memory precursors

2021 ◽  
Author(s):  
Sarah Adamo ◽  
Jan Michler ◽  
Yves Zurbuchen ◽  
Carlo Cervia ◽  
Patrick Taeschler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Acute Infection ◽  
Mammalian Target Of Rapamycin ◽  
Cell Receptor ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Transcriptional Signature ◽  
One Year

Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8+ T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting one year after acute infection re-express CD45RA and interleukin-7 receptor alpha (CD127), upregulate T cell factor-1 (TCF1), and maintain low CCR7, thus resembling CD45RA+ effector-memory T (TEMRA) cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clone contraction and disappearance. Collectively, we identify a transcriptional signature differentiating short- from long-lived memory CD8+ T cells following an acute virus infection in humans.

Antigen cross-presentation in the liver generates protective memory CD8+ T cells in the absence of inflammation

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
JP Böttcher ◽  
D Stabenow ◽  
S Debey-Pascher ◽  
A Staratschek-Jox ◽  
J Grell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Cross Presentation
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