High-Dimensional Analysis of Human CD8+ T Cell Phenotype, Function, and Antigen Specificity

2013 ◽  
pp. 61-84 ◽  
Author(s):  
Evan W. Newell ◽  
Wenyu Lin
Keyword(s):  
T Cell ◽  
Dimensional Analysis ◽  
Cd8 T Cell ◽  
High Dimensional ◽  
Cell Phenotype ◽  
Antigen Specificity

High dimensional analysis defines multicytokine T‐cell subsets and supports a role for IL‐21 in atopic dermatitis

Allergy ◽  
2021 ◽  
Author(s):  
Tali Czarnowicki ◽  
Hyun Je Kim ◽  
Axel P Villani ◽  
Jacob Glickman ◽  
Ester Del Duca ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
T Cell ◽  
Dimensional Analysis ◽  
T Cell Subsets ◽  
High Dimensional

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 IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection

2016 ◽  
Vol 213 (7) ◽  
pp. 1319-1329 ◽  
Author(s):  
Kristin R. Renkema ◽  
June-Yong Lee ◽  
You Jeong Lee ◽  
Sara E. Hamilton ◽  
Kristin A. Hogquist ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Antigen Specificity ◽  
Th1 Cell ◽  
Memory Cd8 T Cells ◽  
Expression Levels ◽  
Cell Pool

Previous studies have revealed that a population of innate memory CD8+ T cells is generated in response to IL-4, first appearing in the thymus and bearing high expression levels of Eomesodermin (Eomes) but not T-bet. However, the antigen specificity and functional properties of these cells is poorly defined. In this study, we show that IL-4 regulates not only the frequency and function of innate memory CD8+ T cells, but also regulates Eomes expression levels and functional reactivity of naive CD8+ T cells. Lack of IL-4 responsiveness attenuates the capacity of CD8+ T cells to mount a robust response to lymphocytic choriomeningitis virus infection, with both quantitative and qualitative effects on effector and memory antigen-specific CD8+ T cells. Unexpectedly, we found that, although numerically rare, memory phenotype CD8+ T cells in IL-4Rα–deficient mice exhibited enhanced reactivity after in vitro and in vivo stimulation. Importantly, our data revealed that these effects of IL-4 exposure occur before, not during, infection. Together, these data show that IL-4 influences the entire peripheral CD8+ T cell pool, influencing expression of T-box transcription factors, functional reactivity, and the capacity to respond to infection. These findings indicate that IL-4, a canonical Th2 cell cytokine, can sometimes promote rather than impair Th1 cell–type immune responses.

scholarly journals EBV-Specific CD8+T Cell Memory: Relationships Between Epitope Specificity, Cell Phenotype, and Immediate Effector Function

2001 ◽  
Vol 167 (4) ◽  
pp. 2019-2029 ◽  
Author(s):  
Andrew D. Hislop ◽  
Nancy H. Gudgeon ◽  
Margaret F. C. Callan ◽  
Chrysoula Fazou ◽  
Hitoshi Hasegawa ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Effector Function ◽  
T Cell Memory ◽  
Cell Phenotype ◽  
Cell Memory ◽  
Epitope Specificity ◽  
Cd8 T Cell Memory

scholarly journals Bromodomain protein BRD4 directs and sustains CD8 T cell differentiation during infection

2021 ◽  
Vol 218 (8) ◽  
Author(s):  
J. Justin Milner ◽  
Clara Toma ◽  
Sara Quon ◽  
Kyla Omilusik ◽  
Nicole E. Scharping ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Small Molecule ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
Cell Phenotype ◽  
Effector T Cell ◽  
Terminal Effector

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector–specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule–mediated BET inhibition impaired maintenance of a terminal effector T cell phenotype. BRD4 was also required for terminal differentiation of CD8 T cells in the tumor microenvironment in murine models, which we show has implications for immunotherapies. Taken together, these data reveal an unappreciated requirement for BRD4 in coordinating activity of cis regulatory elements to control CD8 T cell fate and lineage stability.

scholarly journals CD8+ T Cells in GCA and GPA: Bystanders or Active Contributors?

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosanne D. Reitsema ◽  
Annemieke M. H. Boots ◽  
Kornelis S. M. van der Geest ◽  
Maria Sandovici ◽  
Peter Heeringa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Blood Vessels ◽  
Cd8 T Cells ◽  
Current Knowledge ◽  
Adaptive Immune Response ◽  
Cd8 T Cell ◽  
Cell Phenotype ◽  
Functional Features ◽  
And Function

Vasculitis refers to inflammation of blood vessels and can cause a variety of serious complications depending on which vessels are affected. Two different forms of vasculitis are Giant Cell Arteritis (GCA) and Granulomatosis with Polyangiitis (GPA). GCA is the most common form of vasculitis in adults affecting the large arteries and can lead to visual impairment and development of aneurysms. GPA affects small- and medium-sized blood vessels predominantly in the lungs and kidneys resulting in organ failure. Both diseases can potentially be fatal. Although the pathogenesis of GCA and GPA are incompletely understood, a prominent role for CD4+ T cells has been implicated in both diseases. More recently, the role of CD8+ T cells has gained renewed interest. CD8+ T cells are important players in the adaptive immune response against intracellular microorganisms. After a general introduction on the different forms of vasculitis and their association with infections and CD8+ T cells, we review the current knowledge on CD8+ T-cell involvement in the immunopathogenesis of GCA and GPA focusing on phenotypic and functional features of circulating and lesional CD8+ T cells. Furthermore, we discuss to which extent aging is associated with CD8+ T-cell phenotype and function in GCA and GPA.

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