scholarly journals Association of Polymorphisms in T-Cell Activation Costimulatory/Inhibitory Signal Genes With Allograft Kidney Rejection Risk

2021 ◽  
Vol 12 ◽  
Author(s):  
Jose Luis Santiago ◽  
Luis Sánchez-Pérez ◽  
Isabel Pérez-Flores ◽  
Maria Angeles Moreno de la Higuera ◽  
Natividad Calvo Romero ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Induction Therapy ◽  
Cell Activation ◽  
Critical Role ◽  
Cell Immune Response ◽  
Nucleotide Polymorphisms ◽  
Antibody Mediated Rejection ◽  
Allograft Kidney

The genes CD28, CD86 and CTLA-4 conform the costimulatory (CD28-CD86) or inhibitory (CTLA-4-CD86) signal in T-cell activation. T-cell immune response has a critical role in allograft rejection, and single nucleotide polymorphisms (SNPs) located in these genes have been widely analyzed with controversial results. We analyzed a group of SNPs located in the three genes: CD28: rs3116496; CD86: rs1129055; and CTLA-4: rs231775 and rs3087243 in a cohort of 632 consecutively recruited kidney transplanted subjects. All polymorphisms were genotyped by TaqMan chemistry and the diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. The analyses showed a statistically significant protective effect to T cell-mediated rejection (TCMR) in carriers of the CTLA-4 rs3087243*G allele, especially in patients with TCMR Banff ≥2 in the overall cohort and in patients without thymoglobulin induction therapy. Both associations were corroborated as independent factors in the multivariate analysis. Interestingly, associations with rejection were not found for any SNP in patients with thymoglobulin induction therapy. As expected, considering the major role of these genes in T-cell activation, no effect was observed for antibody-mediated rejection (ABMR). In conclusion, the SNP rs3087243 located in the CTLA-4 gene may be considered a useful independent biomarker for TCMR risk especially for severe TCMR in patients who did no received thymoglobulin induction therapy.

scholarly journals The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Daiki Mori ◽  
Claude Grégoire ◽  
Guillaume Voisinne ◽  
Javier Celis-Gutierrez ◽  
Rudy Aussel ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Signal Propagation ◽  
Nucleotide Polymorphisms ◽  
Transmembrane Receptors ◽  
Promising Target ◽  
Primary Mouse ◽  
Respective Contribution

To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9–based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes.

scholarly journals Annexin A5 is essential for PKCθ translocation during T-cell activation

2020 ◽  
Vol 295 (41) ◽  
pp. 14214-14221
Author(s):  
Zhaoqing Hu ◽  
Lin Li ◽  
Banghui Zhu ◽  
Yi Huang ◽  
Xinran Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Adaptive Immune System ◽  
Annexin A5 ◽  
Activated T Cells ◽  
Calcium Dependent

T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been reported to mediate PKCδ activation by interaction with PKCδ, a homologue of PKCθ, which implicates a potential role of ANXA5 involved in PKCθ signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKCθ to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKCθ upon TCR engagement and blocked the recruitment of CARMA1-BCL10-MALT1 signalosome, which provides a platform for the catalytic activation of IKKs and subsequent activation of canonical NF-κB signaling in activated T cells. As a result, NF-κB activation was impaired in ANXA5-KO T cells. T-cell activation was also suppressed by ANAX5 knockdown in primary T cells. These results demonstrated a novel role of ANXA5 in PKC translocation and PKC signaling during T-cell activation.

Bidirectional Effects of Corticosterone on Splenic T-Cell Activation: Critical Role of Cell Density and Culture Time

2001 ◽  
Vol 73 (2) ◽  
pp. 139-148 ◽  
Author(s):  
G. Jan Wiegers ◽  
Ilona E.M. Stec ◽  
Wolfgang E.F. Klinkert ◽  
Astrid C.E. Linthorst ◽  
Johannes M.H.M. Reul
Keyword(s):  
T Cell ◽  
Cell Density ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Culture Time ◽  
Bidirectional Effects

Critical role of ROCK2 activity in facilitating mucosal CD4 + T cell activation in inflammatory bowel disease

2018 ◽  
Vol 89 ◽  
pp. 125-138 ◽  
Author(s):  
Wenjing Yang ◽  
Guangxi Zhou ◽  
Tianming Yu ◽  
Liang Chen ◽  
Lin Yu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
T Cell Activation ◽  
Bowel Disease ◽  
Cell Activation ◽  
Critical Role ◽  
Cd4 T Cell ◽  
Inflammatory Bowel

scholarly journals CD8+ T Cells in Atherosclerosis

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 37
Author(s):  
Sarah Schäfer ◽  
Alma Zernecke
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Critical Role ◽  
Cd8 T Cell ◽  
Immune Checkpoints ◽  
Cell Functions

Atherosclerotic lesions are populated by cells of the innate and adaptive immune system, including CD8+ T cells. The CD8+ T cell infiltrate has recently been characterized in mouse and human atherosclerosis and revealed activated, cytotoxic, and possibly dysfunctional and exhausted cell phenotypes. In mouse models of atherosclerosis, antibody-mediated depletion of CD8+ T cells ameliorates atherosclerosis. CD8+ T cells control monopoiesis and macrophage accumulation in early atherosclerosis. In addition, CD8+ T cells exert cytotoxic functions in atherosclerotic plaques and contribute to macrophage cell death and necrotic core formation. CD8+ T cell activation may be antigen-specific, and epitopes of atherosclerosis-relevant antigens may be targets of CD8+ T cells and their cytotoxic activity. CD8+ T cell functions are tightly controlled by costimulatory and coinhibitory immune checkpoints. Subsets of regulatory CD25+CD8+ T cells with immunosuppressive functions can inhibit atherosclerosis. Importantly, local cytotoxic CD8+ T cell responses may trigger endothelial damage and plaque erosion in acute coronary syndromes. Understanding the complex role of CD8+ T cells in atherosclerosis may pave the way for defining novel treatment approaches in atherosclerosis. In this review article, we discuss these aspects, highlighting the emerging and critical role of CD8+ T cells in atherosclerosis.

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