Response of naïve and memory CD8+ T cells to antigen stimulation in vivo

10.1038/76907 ◽  
2000 ◽  
Vol 1 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Henrique Veiga-Fernandes ◽  
Ulrich Walter ◽  
Christine Bourgeois ◽  
Angela McLean ◽  
Benedita Rocha
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Antigen Stimulation

scholarly journals p53 Hinders CRISPR/Cas9-Mediated Targeted Gene Disruption in Memory CD8 T Cells In Vivo

2020 ◽  
Vol 205 (8) ◽  
pp. 2222-2230
Author(s):  
Samarchith P. Kurup ◽  
Steven J. Moioffer ◽  
Lecia L. Pewe ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Gene Disruption ◽  
Memory Cd8 T Cells ◽  
Targeted Gene Disruption

scholarly journals Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis

2017 ◽  
Vol 214 (6) ◽  
pp. 1593-1606 ◽  
Author(s):  
Hossam A. Abdelsamed ◽  
Ardiana Moustaki ◽  
Yiping Fan ◽  
Pranay Dogra ◽  
Hazem E. Ghoneim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Human Memory ◽  
Memory Cd8 T Cells ◽  
Memory Cd8 T Cell ◽  
Cell Effector

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired TEM-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.

scholarly journals PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

2006 ◽  
Vol 203 (10) ◽  
pp. 2281-2292 ◽  
Author(s):  
Constantinos Petrovas ◽  
Joseph P. Casazza ◽  
Jason M. Brenchley ◽  
David A. Price ◽  
Emma Gostick ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Antigen Specificity ◽  
Chronic Infections ◽  
Human Virus ◽  
Memory Cd8 T Cells ◽  
Persistent Virus

Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8+ T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8+ T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8+ T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8+ T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8+ T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo.

scholarly journals In vivo rescue of defective memory CD8+T cells by cognate helper T cells

2005 ◽  
Vol 78 (4) ◽  
pp. 879-887 ◽  
Author(s):  
Udayasankar Kumaraguru ◽  
Kaustuv Banerjee ◽  
Barry T. Rouse
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Helper T Cells ◽  
Memory Cd8 T Cells

scholarly journals Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation

2014 ◽  
Vol 211 (2) ◽  
pp. 345-356 ◽  
Author(s):  
Erin R. Mehlhop-Williams ◽  
Michael J. Bevan
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
Protein Tyrosine Phosphatases ◽  
Central Memory ◽  
Naive T Cells ◽  
Memory Cd8 T Cells ◽  
Naïve T Cells

A hallmark of immunological memory is the ability of previously primed T cells to undergo rapid recall responses upon antigen reencounter. Classic work has suggested that memory T cells proliferate in response to lower doses of antigen than naive T cells and with reduced requirements for co-stimulation. In contrast to this premise, we observed that naive but not memory T cells proliferate in vivo in response to limited antigen presentation. To reconcile these observations, we tested the antigen threshold requirement for cell cycle entry in naive and central memory CD8+ T cells. Although both naive and memory T cells detect low dose antigen, only naive T cells activate cell cycle effectors. Direct comparison of TCR signaling on a single cell basis indicated that central memory T cells do not activate Zap70, induce cMyc expression, or degrade p27 in response to antigen levels that activate these functions in naive T cells. The reduced sensitivity of memory T cells may result from both decreased surface TCR expression and increased expression of protein tyrosine phosphatases as compared with naive T cells. Our data describe a novel aspect of memory T cell antigen threshold sensitivity that may critically regulate recall expansion.

scholarly journals Overexpression of IL-15 In Vivo Increases Antigen-Driven Memory CD8+ T Cells Following a Microbe Exposure

2002 ◽  
Vol 168 (3) ◽  
pp. 1198-1203 ◽  
Author(s):  
Toshiki Yajima ◽  
Hitoshi Nishimura ◽  
Ryotaro Ishimitsu ◽  
Taketo Watase ◽  
Dirk H. Busch ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells

scholarly journals Differential Sensitivity of Naive and Memory CD8+T Cells to Apoptosis in Vivo

2002 ◽  
Vol 169 (7) ◽  
pp. 3760-3770 ◽  
Author(s):  
Jason M. Grayson ◽  
Laurie E. Harrington ◽  
J. Gibson Lanier ◽  
E. John Wherry ◽  
Rafi Ahmed
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Differential Sensitivity ◽  
Memory Cd8 T Cells

In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells

Vaccine ◽  
2017 ◽  
Vol 35 (52) ◽  
pp. 7240-7249 ◽  
Author(s):  
Natiely S. Sales ◽  
Jamile R. Silva ◽  
Luana R.M.M. Aps ◽  
Mariângela O. Silva ◽  
Bruna F.M.M. Porchia ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papilloma Virus ◽  
Cd8 T Cells ◽  
Effector Memory ◽  
In Vivo Electroporation ◽  
Papilloma Virus ◽  
Memory Cd8 T Cells ◽  
Therapeutic Control ◽  
Associated Tumors

scholarly journals Estimating In Vivo Death Rates of Targets due to CD8 T-Cell-Mediated Killing

2008 ◽  
Vol 82 (23) ◽  
pp. 11749-11757 ◽  
Author(s):  
Vitaly V. Ganusov ◽  
Rob J. De Boer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Bacterial Infections ◽  
Cytotoxic T Lymphocyte ◽  
Cd8 T Cell ◽  
Target Cells ◽  
Published Data ◽  
Memory Cd8 T Cells

ABSTRACT Despite recent advances in immunology, several key parameters determining virus dynamics in infected hosts remain largely unknown. For example, the rate at which specific effector and memory CD8 T cells clear virus-infected cells in vivo is hardly known for any viral infection. We propose a framework to quantify T-cell-mediated killing of infected or peptide-pulsed target cells using the widely used in vivo cytotoxicity assay. We have reanalyzed recently published data on killing of peptide-pulsed splenocytes by cytotoxic T lymphocytes and memory CD8 T cells specific to NP396 and GP276 epitopes of lymphocytic choriomeningitis virus (LCMV) in the mouse spleen. Because there are so many effector CD8 T cells in spleens of mice at the peak of the immune response, NP396- and GP276-pulsed targets are estimated to have very short half-lives of 2 and 14 min, respectively. After the effector numbers have diminished, i.e., in LCMV-immune mice, the half-lives become 48 min and 2.8 h for NP396- and GP276-expressing targets, respectively. Analysis of several alternative models demonstrates that the estimates of half-life times of peptide-pulsed targets are not affected when changes are made in the model assumptions. Our report provides a unifying framework to compare killing efficacies of CD8 T-cell responses specific to different viral and bacterial infections in vivo, which may be used to compare efficacies of various cytotoxic-T-lymphocyte-based vaccines.

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