Macroautophagy Regulates Energy Metabolism during Effector T Cell Activation

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

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Generation and biochemical analysis of human effector CD4 T cells: alterations in tyrosine phosphorylation and loss of CD3ζ expression

Blood ◽

10.1182/blood.v97.12.3851 ◽

2001 ◽

Vol 97 (12) ◽

pp. 3851-3859 ◽

Cited By ~ 44

Author(s):

Sandeep Krishnan ◽

Vishal G. Warke ◽

Madhusoodana P. Nambiar ◽

Henry K. Wong ◽

George C. Tsokos ◽

...

Keyword(s):

T Cells ◽

Cell Differentiation ◽

T Cell ◽

Tyrosine Phosphorylation ◽

T Cell Activation ◽

Cd4 T Cells ◽

Cell Activation ◽

Effector T Cells ◽

T Cell Differentiation ◽

Effector T Cell

Human effector T cells have been difficult to isolate and characterize due to their phenotypic and functional similarity to the memory subset. In this study, a biochemical approach was used to analyze human effector CD4 T cells generated in vitro by activation with anti-CD3 and autologous monocytes for 3 to 5 days. The resultant effector cells expressed the appropriate activation/differentiation markers and secreted high levels of interferon γ (IFN-γ) when restimulated. Biochemically, effector CD4 T cells exhibited increases in total intracellular tyrosine phosphorylation and effector-associated phosphorylated species. Paradoxically, these alterations in tyrosine phosphorylation were concomitant with greatly reduced expression of CD3ζ and CD3ε signaling subunits coincident with a reduction in surface T-cell receptor (TCR) expression. Because loss of CD3ζ has also been detected in T cells isolated ex vivo from individuals with cancer, chronic viral infection, and autoimmune diseases, the requirements and kinetics of CD3ζ down-regulation were examined. The loss of CD3ζ expression persisted throughout the course of effector T-cell differentiation, was reversible on removal from the activating stimulus, and was modulated by activation conditions. These biochemical changes occurred in effector T cells generated from naive or memory CD4 T-cell precursors and distinguished effector from memory T cells. The results suggest that human effector T-cell differentiation is accompanied by alterations in the TCR signal transduction and that loss of CD3ζ expression may be a feature of chronic T-cell activation and effector generation in vivo.

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Regulatory T cells sense effector T‐cell activation through synchronized JunB expression

FEBS Letters ◽

10.1002/1873-3468.13393 ◽

2019 ◽

Vol 593 (10) ◽

pp. 1020-1029 ◽

Cited By ~ 2

Author(s):

Jingxia Wu ◽

Sicong Ma ◽

Agnes Hotz‐Wagenblatt ◽

Peter Angel ◽

Kerstin Mohr ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

T Cell Activation ◽

Cell Activation ◽

Effector T Cell

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Autoimmunity during Thymectomy-Induced Lymphopenia: Role of Thymus Ablation and Initial Effector T Cell Activation Timing in Nonobese Diabetic Mice

The Journal of Immunology ◽

10.4049/jimmunol.0901954 ◽

2009 ◽

Vol 183 (8) ◽

pp. 4913-4920 ◽

Cited By ~ 17

Author(s):

Marie-Claude Gagnerault ◽

Olivia Lanvin ◽

Virginie Pasquier ◽

Corinne Garcia ◽

Diane Damotte ◽

...

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Diabetic Mice ◽

Effector T Cell ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice

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Juzentaihoto Exerts Anti-Allergic Effects by Inhibiting Effector T-Cell Activation and Inducing and/or Activating Regulatory T Cells in a Murine Model of Contact Hypersensitivity

International Archives of Allergy and Immunology ◽

10.1159/000518448 ◽

2021 ◽

pp. 1-13

Author(s):

Atsushi Tsuge ◽

Sho Yonekura ◽

Satomi Watanabe ◽

Yuta Kurosaki ◽

Shinsuke Hisaka ◽

...

Keyword(s):

T Cells ◽

Monoclonal Antibodies ◽

T Cell ◽

Regulatory T Cells ◽

T Cell Activation ◽

Cell Activation ◽

Effector T Cells ◽

Contact Hypersensitivity ◽

Dependent Manner ◽

Effector T Cell

Background: Juzentaihoto (JTT) is a Kampo prescription that has been used clinically for treating skin diseases such as atopic dermatitis in Japan. We have previously studied the anti-allergic effects of JTT on 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) in mice and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying the anti-allergic actions of JTT is obscure. Methods: We investigated the mechanism underlying the anti-allergic effects of JTT using a TNCB-induced murine CHS model and adoptive cell transfer experiments. Results: We showed that the anti-allergic effects of JTT are due to inhibition of effector T-cell activation and induction and/or activation of regulatory T cells. Furthermore, ex vivo experiments confirmed the effect of JTT on the activation of effector T cells and regulatory T cells, as interferon-γ production decreased, whereas interleukin (IL)-10 production increased, in the cultured lymphocytes obtained from 5% TNCB-sensitized mice treated with anti-CD3ε and anti-CD28 monoclonal antibodies. Flow cytometry showed that the CD4+CD25+Foxp3+, CD4+CD25+Foxp3−, and CD8+CD122+ cell population increased after oral administration of JTT. Finally, the anti-allergic effect of JTT by inducing and/or activating regulatory T cells (Tregs) was confirmed to be mediated by IL-10 through in vivo neutralization experiments with anti-IL-10 monoclonal antibodies. Conclusion: We suggested that JTT exerts anti-allergic effects by regulating the activation of effector T cells and Tregs involved in murine CHS model.

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