scholarly journals A retinoic acid–dependent checkpoint in the development of CD4+ T cell–mediated immunity

2011 ◽  
Vol 208 (9) ◽  
pp. 1767-1775 ◽  
Author(s):  
Karina Pino-Lagos ◽  
Yanxia Guo ◽  
Chrysothemis Brown ◽  
Matthew P. Alexander ◽  
Raúl Elgueta ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
T Cell ◽  
Cd4 T Cell ◽  
Whole Body ◽  
Cell Mediated Immunity ◽  
Whole Body Imaging ◽  
New Perspective ◽  
Cell Effector Function ◽  
Cell Effector

It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4+ T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4+ T cell differentiation and immunity.

IL-1R, WNT and γ-C Cytokine Receptor Signaling Correlate with CD4 T Cell Effector Function in Response to Anti-DEC205-HIV gag p24/polyICLC Vaccination

2014 ◽  
Vol 30 (S1) ◽  
pp. A250-A251
Author(s):  
Khader Ghneim ◽  
Marina Caskey ◽  
Christine Trumpfheller ◽  
Gaelle Breton ◽  
Petra Stafova ◽  
...  
Keyword(s):  
T Cell ◽  
Effector Function ◽  
Cytokine Receptor ◽  
Cd4 T Cell ◽  
Receptor Signaling ◽  
Cell Effector Function ◽  
Cell Effector

scholarly journals 1061The Role of CD4 T Cell Mediated Immunity in Pandemic Influenza Protection

2014 ◽  
Vol 1 (suppl_1) ◽  
pp. S311-S311
Author(s):  
Jennifer Nayak ◽  
Andrea Sant ◽  
Shabnam Alam
Keyword(s):  
T Cell ◽  
Pandemic Influenza ◽  
Cd4 T Cell ◽  
Cell Mediated Immunity

scholarly journals Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets

2016 ◽  
Vol 213 (8) ◽  
pp. 1589-1608 ◽  
Author(s):  
Cindy S. Ma ◽  
Natalie Wong ◽  
Geetha Rao ◽  
Akira Nguyen ◽  
Danielle T. Avery ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathways ◽  
Cd4 T Cells ◽  
Clinical Manifestations ◽  
Effector Function ◽  
Cd4 T Cell ◽  
The Impact ◽  
Cell Effector Function ◽  
Cell Effector

Naive CD4+ T cells differentiate into specific effector subsets—Th1, Th2, Th17, and T follicular helper (Tfh)—that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4+ T cell differentiation in vitro. IL12Rβ1/TYK2 and IFN-γR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10–secreting cells. IL12Rβ1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4+ T cell effector function in the settings of infection, vaccination, or immune dysregulation.

scholarly journals Protein kinase 2 (CK2) controls CD4+ T cell effector function in the pathogenesis of colitis

2020 ◽  
Vol 13 (5) ◽  
pp. 788-798 ◽  
Author(s):  
Wei Yang ◽  
Sara A. Gibson ◽  
Zhaoqi Yan ◽  
Hairong Wei ◽  
Jiahui Tao ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
Effector Function ◽  
Cd4 T Cell ◽  
Cell Effector Function ◽  
Cell Effector

scholarly journals Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3673-3681 ◽  
Author(s):  
Philip O. Scumpia ◽  
Matthew J. Delano ◽  
Kindra M. Kelly-Scumpia ◽  
Jason S. Weinstein ◽  
James L. Wynn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Immune Dysfunction ◽  
Effector Function ◽  
Cd4 T Cell ◽  
Agonistic Antibody ◽  
Adaptive Immune ◽  
Cell Effector Function ◽  
Cell Effector

Abstract Apoptosis of CD4+ T cells and TH2 polarization are hallmarks of sepsis-induced immunoparalysis. In this study, we characterized sepsis-induced adaptive immune dysfunction and examined whether improving T-cell effector function can improve outcome to sepsis. We found that septic mice produced less antigen-specific T-cell–dependent IgM and IgG2a antibodies than sham-treated mice. As early as 24 hours after sepsis, CD4+ T cells proliferated poorly to T-cell receptor stimulation, despite normal responses to phorbol myristate acetate and ionomycin, and possessed decreased levels of CD3ζ. Five days following immunization, CD4+ T cells from septic mice displayed decreased antigen-specific proliferation and production of IL-2 and IFN-γ but showed no difference in IL-4, IL-5, or IL-10 production. Treatment of mice with anti-GITR agonistic antibody restored CD4+ T-cell proliferation, increased TH1 and TH2 cytokine production, partially prevented CD3ζ down-regulation, decreased bacteremia, and increased sepsis survival. Depletion of CD4+ T cells but not CD25+ regulatory T cells eliminated the survival benefit of anti-GITR treatment. These results indicate that CD4+ T-cell dysfunction is a key component of sepsis and that improving T-cell effector function may be protective against sepsis-associated immunoparalysis.

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