No Evidence for Drug-Specific Activation of Circulating T Cells from Patients with HLA-DRB1*07:01-Restricted Lapatinib-Induced Liver Injury

2016 ◽  
Vol 29 (12) ◽  
pp. 2111-2113 ◽  
Author(s):  
Lee Faulkner ◽  
Xiaoli Meng ◽  
Dean J. Naisbitt ◽  
Colin F. Spraggs ◽  
B. Kevin Park
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Circulating T Cells

scholarly journals Mechanisms of Hepatocellular Injury in Hepatitis A

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 861
Author(s):  
Minghang Wang ◽  
Zongdi Feng
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Hepatitis A ◽  
Acute Viral Hepatitis ◽  
Hepatitis A Virus ◽  
Current Knowledge ◽  
Cytotoxic T Cells ◽  
Host Factors ◽  
Hepatocellular Injury

Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8+ T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.

scholarly journals Mesenchymal stem cells alleviate experimental immune-mediated liver injury via chitinase 3-like protein 1-mediated T cell suppression

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Qiuli Liu ◽  
Xiaoyong Chen ◽  
Chang Liu ◽  
Lijie Pan ◽  
Xinmei Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Liver Injury ◽  
T Cell Activation ◽  
Gene Set Enrichment Analysis ◽  
Human Umbilical Cord ◽  
Con A ◽  
Immune Mediated

AbstractLiver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here. We found that CHI3L1 was highly expressed in human umbilical cord MSCs (hUC-MSCs). Downregulating CHI3L1 mitigated the ability of hUC-MSCs to inhibit T cell activation, proliferation and inflammatory cytokine secretion in vitro. Using Concanavalin A (Con A)-induced liver injury mouse model, we found that silencing CHI3L1 significantly abrogated the hUC-MSCs-mediated alleviation of liver injury, accompanying by weakened suppressive effects on infiltration and activation of hepatic T cells, and secretion of pro-inflammatory cytokines. In addition, recombinant CHI3L1 (rCHI3L1) administration inhibited the proliferation and function of activated T cells, and alleviated the Con A-induced liver injury in mice. Mechanistically, gene set enrichment analysis showed that JAK/STAT signalling pathway was one of the most significantly enriched gene pathways in T cells co-cultured with hUC-MSCs with CHI3L1 knockdown, and further study revealed that CHI3L1 secreted by hUC-MSCs inhibited the STAT1/3 signalling in T cells by upregulating peroxisome proliferator-activated receptor δ (PPARδ). Collectively, our data showed that CHI3L1 was a novel MSC-secreted immunosuppressive factor and provided new insights into therapeutic treatment of immune-mediated liver injury.

scholarly journals Marked changes in innate immunity associated with a mild course of COVID-19 in identical twins with athymia and absent circulating T cells

2020 ◽  
Author(s):  
Argentina Colmenero-Velázquez ◽  
Gloria Esteso ◽  
Teresa del Rosal ◽  
Ane Calvo Apalategui ◽  
Hugh Reyburn ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Identical Twins ◽  
Circulating T Cells

Interferon-β1a does not reduce expression of CCR5 and CXCR3 on circulating T cells

2003 ◽  
Vol 141 (1-2) ◽  
pp. 150-154 ◽  
Author(s):  
Pia Kivisäkk ◽  
Anne C. Cotleur ◽  
Jar-Chi Lee ◽  
Richard A. Rudick ◽  
Richard M. Ransohoff
Keyword(s):  
T Cells ◽  
Circulating T Cells

Dregea volubilisAmeliorates Concanavalin A-Induced Liver Injury by Facilitating Apoptosis of Activated T Cells

2008 ◽  
Vol 233 (9) ◽  
pp. 1124-1132 ◽  
Author(s):  
Fangyuan Gong ◽  
Yan Shen ◽  
Chaofeng Zhang ◽  
Jianliang Xu ◽  
Xuefeng Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Injury ◽  
Concanavalin A ◽  
Activated T Cells

Loss of Rt6 Message and Most Circulating T Cells after Thymectomy of Diabetes Prone BB Rats

Autoimmunity ◽  
1994 ◽  
Vol 18 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Probir Sarkar ◽  
Laura Crisá ◽  
Una McKeever ◽  
Rita Bortell ◽  
Eugene Handler ◽  
...  
Keyword(s):  
T Cells ◽  
Bb Rats ◽  
Circulating T Cells

TRMmaintenance is regulated by tissue damage via P2RX7

2018 ◽  
Vol 3 (30) ◽  
pp. eaau1022 ◽  
Author(s):  
Regina Stark ◽  
Thomas H. Wesselink ◽  
Felix M. Behr ◽  
Natasja A. M. Kragten ◽  
Ramon Arens ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Tissue Damage ◽  
Extracellular Nucleotides ◽  
Critical Pathway ◽  
Rna Profiling ◽  
Molecular Pattern ◽  
History Of ◽  
Circulating T Cells

Tissue-resident memory T cells (TRM) are noncirculating immune cells that contribute to the first line of local defense against reinfections. Their location at hotspots of pathogen encounter frequently exposes TRM to tissue damage. This history of danger-signal exposure is an important aspect of TRM-mediated immunity that has been overlooked so far. RNA profiling revealed that TRM from liver and small intestine express P2RX7, a damage/danger-associated molecular pattern (DAMP) receptor that is triggered by extracellular nucleotides (ATP, NAD+). We confirmed that P2RX7 protein was expressed in CD8+ TRM but not in circulating T cells (TCIRC) across different infection models. Tissue damage induced during routine isolation of liver lymphocytes led to P2RX7 activation and resulted in selective cell death of TRM. P2RX7 activation in vivo by exogenous NAD+ led to a specific depletion of TRM while retaining TCIRC. The effect was absent in P2RX7-deficient mice and after P2RX7 blockade. TCR triggering down-regulated P2RX7 expression and made TRM resistant to NAD-induced cell death. Physiological triggering of P2RX7 by sterile tissue damage during acetaminophen-induced liver injury led to a loss of previously acquired pathogen-specific local TRM in wild-type but not in P2RX7 KO T cells. Our results highlight P2RX7-mediated signaling as a critical pathway for the regulation of TRM maintenance. Extracellular nucleotides released during infection and tissue damage could deplete TRM locally and free niches for new and infection-relevant specificities. This suggests that the recognition of tissue damage promotes persistence of antigen-specific over bystander TRM in the tissue niche.

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