scholarly journals CD8 T Cell Tolerance to a Tumor-Associated Self-Antigen Is Reversed by CD4 T Cells Engineered To Express the Same T Cell Receptor

2014 ◽  
Vol 194 (3) ◽  
pp. 1080-1089 ◽  
Author(s):  
Sara Ghorashian ◽  
Pedro Veliça ◽  
Ignatius Chua ◽  
Anne-Marie McNicol ◽  
Ben Carpenter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Self Antigen

scholarly journals Peripheral CD8+ T Cell Tolerance to Self-Proteins Is Regulated Proximally at the T Cell Receptor

Immunity ◽  
2008 ◽  
Vol 28 (5) ◽  
pp. 662-674 ◽  
Author(s):  
Ryan M. Teague ◽  
Philip D. Greenberg ◽  
Carla Fowler ◽  
Maria Z. Huang ◽  
Xiaoxia Tan ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Tolerance ◽  
Cell Tolerance

scholarly journals Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1530
Author(s):  
Sébastien This ◽  
Stefanie F. Valbon ◽  
Marie-Ève Lebel ◽  
Heather J. Melichar
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Regulatory T Cell ◽  
Cell Receptor ◽  
Cell Populations ◽  
T Cell Tolerance ◽  
Receptor Signaling ◽  
Cell Tolerance

The ability of T cells to identify foreign antigens and mount an efficient immune response while limiting activation upon recognition of self and self-associated peptides is critical. Multiple tolerance mechanisms work in concert to prevent the generation and activation of self-reactive T cells. T cell tolerance is tightly regulated, as defects in these processes can lead to devastating disease; a wide variety of autoimmune diseases and, more recently, adverse immune-related events associated with checkpoint blockade immunotherapy have been linked to a breakdown in T cell tolerance. The quantity and quality of antigen receptor signaling depend on a variety of parameters that include T cell receptor affinity and avidity for peptide. Autoreactive T cell fate choices (e.g., deletion, anergy, regulatory T cell development) are highly dependent on the strength of T cell receptor interactions with self-peptide. However, less is known about how differences in the strength of T cell receptor signaling during differentiation influences the ‘function’ and persistence of anergic and regulatory T cell populations. Here, we review the literature on this subject and discuss the clinical implications of how T cell receptor signal strength influences the ‘quality’ of anergic and regulatory T cell populations.

A CD40/CD40L feedback loop drives the breakdown of CD8+T-cell tolerance following depletion of suppressive CD4+T cells

2014 ◽  
Vol 44 (4) ◽  
pp. 1099-1107 ◽  
Author(s):  
Sabine Muth ◽  
Kristian Schütze ◽  
Tobias Hain ◽  
Hideo Yagita ◽  
Hansjörg Schild ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Feedback Loop ◽  
Cd8 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance

scholarly journals Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2713
Author(s):  
Sun-Hye Shin ◽  
Kyung-Ah Cho ◽  
Hee-Soo Yoon ◽  
So-Yeon Kim ◽  
Hee-Yeon Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Acyl Chain ◽  
Signal Strength ◽  
Cell Receptor ◽  
Ceramide Synthase ◽  
Asthmatic Patients

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.

scholarly journals Functional Uncoupling of T-cell Receptor Engagement and Lck Activation in Anergic Human Thymic CD4+T Cells

2001 ◽  
Vol 276 (20) ◽  
pp. 17455-17460 ◽  
Author(s):  
Wakae Fujimaki ◽  
Makio Iwashima ◽  
Junji Yagi ◽  
Hua Zhang ◽  
Hisako Yagi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor
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