scholarly journals Fusobacterium nucleatum CbpF Mediates Inhibition of T Cell Function Through CEACAM1 Activation

2021 ◽  
Vol 11 ◽  
Author(s):  
Johanna Galaski ◽  
Amjad Shhadeh ◽  
Ariana Umaña ◽  
Christopher C. Yoo ◽  
Ludovica Arpinati ◽  
...  
Keyword(s):  
T Cell ◽  
Carcinoembryonic Antigen ◽  
Cell Function ◽  
Surface Protein ◽  
Fusobacterium Nucleatum ◽  
T Cell Response ◽  
Immune Evasion Mechanism ◽  
T Cell Function ◽  
Dependent Inhibition ◽  
Domain Block

F. nucleatum is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that F. nucleatum binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) via the trimeric autotransporter adhesin CbpF. However, whether this binding is functional or whether other fusobacterial trimeric autotransporter adhesins are involved in CEACAM1 activation is unknown. In this study, using F. nucleatum mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that F. nucleatum CbpF binds and activates CEACAM1 and also binds carcinoembryonic antigen (CEA), a tumor-associated protein. We further find that CEACAM antibodies directed against the CEACAM N-terminal domain block the CbpF-CEACAM1 interaction. In functional assays, we demonstrate CbpF-dependent inhibition of CD4+ T cell response. Thus, we characterize an immune evasion mechanism in which F. nucleatum uses its surface protein CbpF to inhibit T cell function by activating CEACAM1.

scholarly journals Tumor-Released Survivin Induces a Type-2 T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro

2012 ◽  
Vol 6 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Jessica M. S. Jutzy ◽  
Salma Khan ◽  
Malyn May Asuncion-Valenzuela ◽  
Terry-Ann M. Milford ◽  
Kimberly J. Payne ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Cell Function ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
T Cell Function

Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Isoforms Alternatively Inhibit and Costimulate Human T Cell Function

2004 ◽  
Vol 172 (6) ◽  
pp. 3535-3543 ◽  
Author(s):  
Daohong Chen ◽  
Hideki Iijima ◽  
Takashi Nagaishi ◽  
Atsushi Nakajima ◽  
Sara Russell ◽  
...  
Keyword(s):  
T Cell ◽  
Carcinoembryonic Antigen ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Cellular Adhesion ◽  
T Cell Function ◽  
Human T Cell ◽  
Cellular Adhesion Molecule

scholarly journals Discovery and characterization of llama VHH targeting the RO form of human CD45

2020 ◽  
Author(s):  
Deepti Rokkam ◽  
Patrick J. Lupardus
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Tyrosine Phosphatase ◽  
Surface Protein ◽  
Cell Receptor ◽  
Phage Display Library ◽  
Signaling Complex ◽  
T Cell Function

AbstractCD45 is an abundant and highly active cell-surface protein tyrosine phosphatase (PTP) found on cells of hematopoietic origin. CD45 is of particular importance for T-cell function, playing a key role in the activation/inactivation cycle of the T-cell receptor signaling complex. The extracellular domain of CD45 is comprised of an N-terminal mucin-like domain which can be alternatively spliced to a core domain (RO) consisting of four domains with fibronectin 3 domain (FN3)-like topology. The study of CD45 has been hampered by a small set of publicly available antibodies, which we characterized as specific to the N-terminal FN3 domains of CD45 RO. To broaden the human CD45 reagent set, we identified anti-CD45 single domain VHH antibodies from a post-immune llama phage display library. Using a yeast display domain mapping system and affinity measurement we characterized seven unique clonotypes specific for CD45 RO, including binders that target each of the four FN3-like domains. These VHH molecules are important new tools for studying the role of CD45 in T-cell function in vitro and in vivo.

Dynamic Changes in Ex Vivo T-Cell Function After Viral Clearance in Chronic HCV Infection

2019 ◽  
Vol 220 (8) ◽  
pp. 1290-1301 ◽  
Author(s):  
Ji Won Han ◽  
Pil Soo Sung ◽  
Kyung Hwan Kim ◽  
Seon-Hui Hong ◽  
Eui-Cheol Shin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Function ◽  
Ex Vivo ◽  
T Cell Response ◽  
Viral Clearance ◽  
Hcv Infection ◽  
T Cell Function ◽  
Chronic Hcv

Abstract Background Direct-acting antiviral (DAA) agents can successfully treat chronic hepatitis C virus (HCV) infection. However, the ex vivo HCV-specific T-cell function following viral clearance remains unknown. Methods We investigated functional alterations and phenotypic changes in ex vivo HCV-specific CD8+ T cells with a longitudinal analysis of 41 patients with chronic HCV infection who were undergoing DAA treatment. Results A patient subset exhibited a significantly increased T-cell response (mainly CD8+ T cells) at week 4 of treatment. However, this increased T-cell response diminished in later weeks. Relative to pretreatment levels, the ex vivo HCV-specific CD8+ T-cell frequency decreased at 12 weeks after the end of treatment, along with a decreased antigen-experienced CD8+ T-cell population. DAA treatment increased the proliferative capacity of HCV-specific CD8+ T cells, but this change was not correlated with ex vivo function. Patients experiencing viral breakthrough or relapse exhibited defective restoration of T-cell function. Conclusion Our present results indicated that DAA-mediated viral clearance only transiently restored ex vivo T-cell function, suggesting a need to enhance T-cell function in DAA-treated patients.

scholarly journals Epitope-Specific Regulatory CD4 T Cells Reduce Virus-Induced Illness while Preserving CD8 T-Cell Effector Function at the Site of Infection

2010 ◽  
Vol 84 (20) ◽  
pp. 10501-10509 ◽  
Author(s):  
Jie Liu ◽  
Tracy J. Ruckwardt ◽  
Man Chen ◽  
John D. Nicewonger ◽  
Teresa R. Johnson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Viral Clearance ◽  
Cd4 T Cell ◽  
T Cell Function ◽  
Specific Subset

ABSTRACT The role of epitope-specific regulatory CD4 T cells in modulating CD8 T-cell-mediated immunopathology during acute viral infection has not been well defined. In the murine model of respiratory syncytial virus (RSV) infection, CD8 T cells play an important role in both viral clearance and immunopathology. We have previously characterized two RSV epitope-specific CD4 T-cell responses with distinct phenotypic properties. One of them, the IAbM209-specific subset, constitutively expresses FoxP3 and modulates CD8 T-cell function in vitro. We show here that the IAbM209-specific CD4 T-cell response regulates CD8 T-cell function in vivo and is associated with diminished RSV-induced illness without affecting viral clearance at the site of infection. Achieving the optimal balance of regulatory and effector T-cell function is an important consideration for designing future vaccines.

Positive effects of glucocorticoids on T cell function and development by upregulation of interleukin-7 receptor α

2001 ◽  
Vol 120 (5) ◽  
pp. A314-A315
Author(s):  
D FRANCHIMONT ◽  
J GALON ◽  
M VACCHIO ◽  
R VISCONTI ◽  
G CHROUSOS ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Positive Effects ◽  
Interleukin 7 ◽  
T Cell Function
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