scholarly journals Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes

2007 ◽  
Vol 204 (9) ◽  
pp. 2075-2087 ◽  
Author(s):  
Emilie Narni-Mancinelli ◽  
Laura Campisi ◽  
Delphine Bassand ◽  
Julie Cazareth ◽  
Pierre Gounon ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Secondary Infection ◽  
Interferon Γ ◽  
Phagocytic Cells ◽  
Oxygen Intermediates ◽  
Therapeutic Vaccines ◽  
Memory Cd8 T Cells ◽  
Tnf Α

Cytolysis, interferon γ and tumor necrosis factor (TNF) α secretion are major effector mechanisms of memory CD8+ T cells that are believed to be required for immunological protection in vivo. By using mutants of the intracellular bacterium Listeria monocytogenes, we found that none of these effector activities is sufficient to protect against secondary infection with wild-type (WT) bacteria. We demonstrated that CCL3 derived from reactivated memory CD8+ T cells is required for efficient killing of WT bacteria. CCL3 induces a rapid TNF-α secretion by innate inflammatory mononuclear phagocytic cells (MPCs), which further promotes the production of radical oxygen intermediates (ROIs) by both MPCs and neutrophils. ROI generation is the final bactericidal mechanism involved in L. monocytogenes clearance. These results therefore uncover two levels of regulation of the antibacterial secondary protective response: (a) an antigen-dependent phase in which memory CD8+ T cells are reactivated and control the activation of the innate immune system, and (b) an antigen-independent phase in which the MPCs coordinate innate immunity and promote the bactericidal effector activities. In this context, CCL3-secreting memory CD8+ T cells are able to mediate “bystander” killing of an unrelated pathogen upon antigen-specific reactivation, a mechanism that may be important for the design of therapeutic vaccines.

scholarly journals Resident memory CD8 T cells persist for years in human small intestine

2019 ◽  
Vol 216 (10) ◽  
pp. 2412-2426 ◽  
Author(s):  
Raquel Bartolomé-Casado ◽  
Ole J.B. Landsverk ◽  
Sudhir Kumar Chauhan ◽  
Lisa Richter ◽  
Danh Phung ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
Lamina Propria ◽  
Cd8 T Cells ◽  
Vaccine Development ◽  
Oral Vaccines ◽  
Memory Cd8 T Cells ◽  
Immune Mediated ◽  
Tnf Α ◽  
Bona Fide

Resident memory CD8 T (Trm) cells have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI, we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for >1 yr in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.

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.

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 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 Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis

2017 ◽  
Vol 76 (12) ◽  
pp. 2075-2084 ◽  
Author(s):  
Wen-Xiu Mo ◽  
Shan-Shan Yin ◽  
Hua Chen ◽  
Chen Zhou ◽  
Jia-Xin Zhou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
T Cells ◽  
Disease Activity ◽  
Chemokine Receptors ◽  
Interferon Γ ◽  
Receptor Expression ◽  
Migration Assay ◽  
Tnf Α

ObjectivesTo explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA).MethodsSixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay.ResultsPeripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA.ConclusionsHigh levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA.

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
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