T Cell Apoptosis Induced by Interleukin-2 Deprivation or Transforming Growth Factor-β2: Modulation by the Phosphatase Inhibitors Okadaic Acid and Calyculin A

1995 ◽  
Vol 221 (2) ◽  
pp. 395-403 ◽  
Author(s):  
Michael Weller ◽  
Ursula Malipiero ◽  
Peter Groscurth ◽  
Adriano Fontana
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Okadaic Acid ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Calyculin A ◽  
Phosphatase Inhibitors ◽  
T Cell Apoptosis ◽  
Transforming Growth Factor Β2

scholarly journals Requirement for Transforming Growth Factor β1 in Controlling T Cell Apoptosis

2001 ◽  
Vol 194 (4) ◽  
pp. 439-454 ◽  
Author(s):  
WanJun Chen ◽  
Wenwen Jin ◽  
Hongsheng Tian ◽  
Paula Sicurello ◽  
Mark Frank ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Transforming Growth Factor ◽  
Death Receptor ◽  
Cell Receptor ◽  
Transforming Growth Factor Β1 ◽  
T Cell Apoptosis ◽  
Tgf Β1

Transforming growth factor (TGF)-β1, a potent immunoregulatory molecule, was found to control the life and death decisions of T lymphocytes. Both thymic and peripheral T cell apoptosis was increased in mice lacking TGF-β1 (TGF-β1−/−) compared with wild-type littermates. Engagement of the T cell receptor enhanced this aberrant T cell apoptosis, as did signaling through either the death receptor Fas or the tumor necrosis factor α receptor in peripheral T cells. Strikingly, TGF-β was localized within the mitochondria of normal T cells, and the absence of TGF-β1 resulted in disruption of mitochondrial membrane potential (Δψm), which marks the point of no return in a cell condemned to die. This TGF-β–dependent regulation of viability appears dissociable from the TGF-β1 membrane receptor–Smad3 signaling pathway, but associated with a mitochondrial antiapoptotic protein Bcl–XL. Thus, TGF-β1 may protect T cells at multiple sites in the death pathway, particularly by maintaining the essential integrity of mitochondria. These findings may have broad implications not only for T cell selection and death in immune responses and in the generation of tolerance, but also for defining the mechanisms of programmed cell death in general.

Transforming growth factor-β2 induces apoptosis of murine T cell clones without down-regulatingbcl-2 mRNA expression

1994 ◽  
Vol 24 (6) ◽  
pp. 1293-1300 ◽  
Author(s):  
Michael Weller ◽  
Daniel B. Constam ◽  
Ursula Malipiero ◽  
Adriano Fontana
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
T Cell Clones ◽  
Cell Clones ◽  
Transforming Growth Factor Β2

Targeting Lymphocyte Activation Gene 3 to Reverse T-Lymphocyte Dysfunction and Improve Survival in Murine Polymicrobial Sepsis

2020 ◽  
Vol 222 (6) ◽  
pp. 1051-1061
Author(s):  
Jing-sheng Lou ◽  
Jia-feng Wang ◽  
Miao-miao Fei ◽  
Yan Zhang ◽  
Jun Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Apoptosis ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Interferon Γ ◽  
T Cell Apoptosis ◽  
Cytokine Levels ◽  
Lymphocyte Activation Gene

Abstract Background Lymphocyte activation gene 3 (LAG-3) is one of the immune checkpoint molecules, negatively regulating the T-cell reactions. The present study investigated the role of LAG-3 in sepsis-induced T-lymphocyte disability. Methods Mice sepsis was induced by cecal ligation and puncture (CLP). LAG-3 expression on some immune cells were detected 24 hours after CLP. LAG-3 knockout and anti–LAG-3 antibody were applied to investigate the effects on the survival, bacterial clearance. Cytokine levels, T-cell counts, and the presence of apoptosis (in blood, spleen, and thymus) were also determined. In vitro T-cell apoptosis, interferon γ secretion, and proliferation were measured. The expression of interleukin 2 receptor on T cells was also determined after CLP. Results LAG-3 was up-regulated on CD4+/CD8+ T, CD19+ B, natural killer, CD4+CD25+ regulatory T cells and dendritic cells. Both LAG-3 knockout and anti–LAG-3 antibody had a positive effect on survival and on blood or peritoneal bacterial clearance in mice undergoing CLP. Cytokine levels and T-cell apoptosis decreased in anti–LAG-3 antibody–treated mice. Induced T-cell apoptosis decreased, whereas interferon γ secretion and proliferation were improved by anti–LAG-3 antibody in vitro. Interleukin 2 receptor was up-regulated on T cells in both wild-type and LAG-3–knockout mice undergoing CLP. Conclusions LAG-3 knockout or anti–LAG-3 antibody blockade protected mice undergoing CLP from sepsis-associated immunodysfunction and may be a new target for the treatment.

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