scholarly journals Long‐Term Protease Inhibitor–Containing Therapy Results in Limited Improvement in T Cell Function but Not Restoration of Interleukin‐12 Production in Pediatric Patients with AIDS

2001 ◽  
Vol 184 (2) ◽  
pp. 201-205 ◽  
Author(s):  
Claire Chougnet ◽  
Shirley Jankelevich ◽  
Keith Fowke ◽  
David Liewehr ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
T Cell ◽  
Protease Inhibitor ◽  
Pediatric Patients ◽  
Cell Function ◽  
Interleukin 12 ◽  
T Cell Function

scholarly journals Erratum: Corrigendum: The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
G. Clutton ◽  
Y. Xu ◽  
P. L. Baldoni ◽  
K. R. Mollan ◽  
J. Kirchherr ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Long Term Effects ◽  
T Cell Function ◽  
Short And Long Term ◽  
Hiv 1 ◽  
Reversing Agents

scholarly journals Author response: Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function

2018 ◽  
Author(s):  
Marie Bettonville ◽  
Stefania d'Aria ◽  
Kathleen Weatherly ◽  
Paolo E Porporato ◽  
Jinyu Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Author Response ◽  
T Cell Function

T cell function and activated CD8+38+45RO+ T cells as progression markers in hemophiliacs with long term HIV infection

1997 ◽  
Vol 56 ◽  
pp. 132
Author(s):  
Z. Poulopoulou ◽  
C. Psarra ◽  
V. Kapsimali ◽  
A. Karafoulidou ◽  
O. Katsarou ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cell Function ◽  
T Cell Function ◽  
Progression Markers

Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection

AIDS ◽  
1998 ◽  
Vol 12 (13) ◽  
pp. 1591-1600 ◽  
Author(s):  
Patrizia Carotenuto ◽  
Dennis Looij ◽  
Lian Keldermans ◽  
Frank de Wolf ◽  
Jaap Goudsmit
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Cell Function ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
T Cell Function

Discovery of COM701, a therapeutic antibody targeting the novel immune checkpoint PVRIG, for the treatment of cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3074-3074 ◽  
Author(s):  
Spencer Liang ◽  
Ofer Levy ◽  
Sudipto Ganguly ◽  
Maya Kotturi ◽  
Ilan Vaknin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Wild Type ◽  
High Affinity ◽  
T Cell Function

3074 Background: While inhibitors of CTLA4 and PD1 have emerged as effective cancer therapies, the majority of treated patients do not derive long term benefit. Employing our computational discovery platform, we discovered PVRIG as an immune suppressive molecule expressed on T and NK cells and identified COM701, an antibody (Ab) targeting human PVRIG that enhances T cell function and anti-tumor responses. Methods: Anti-human PVRIG Ab COM701 was identified as an antagonistic Ab that enhanced T cell function in multiple assays. Antagonistic anti-mouse PVRIG Abs and PVRIG deficient (PVRIG-/-) mice were generated and characterized using syngeneic tumor models. Results: PVRIG was induced upon T cell activation, with long term activation leading to the highest expression. PVRL2 was identified as the ligand for PVRIG, placing PVRIG in the DNAM/TIGIT immunoreceptor axis. Compared to normal adjacent tissues, PVRIG and PVRL2 were both induced in the tumor microenvironment of several human cancers. To target PVRIG for therapeutic intervention, we identified COM701, a high affinity Ab that disrupts the interaction of PVRIG with PVRL2. COM701 enhanced CD8 T cell proliferation and IFN-g production in vitro and had an additive or synergistic effect on T cell activation when further combined with an anti-PD1 or anti-TIGIT Ab. Consistent with a checkpoint function for human PVRIG, mouse PVRIG-/- T cells showed increased function compared to wild type T cells. A surrogate antagonistic anti-mPVRIG Ab reduced growth of CT26 and B16 tumors when combined with an anti-PDL1 Ab in vivo. MC38 tumors also grew slower in PVRIG-/- mice compared to wild type mice and ex vivo analysis pointed to functional differences in anti-cancer immunity. Conclusions: We demonstrated that targeting PVRIG with COM701, a high affinity antagonistic Ab, increased human T cell function. We further showed that PVRIG was induced in the tumor microenvironment and that disruption of PVRIG/PVRL2 interaction resulted in reduced tumor growth in preclinical models. These data demonstrate that PVRIG is a promising target for the treatment of cancer and provide the rationale for COM701 as a potential cancer immunotherapy.

scholarly journals Long-term antigen exposure irreversibly modifies metabolic requirements for T cell function

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Marie Bettonville ◽  
Stefania d'Aria ◽  
Kathleen Weatherly ◽  
Paolo E Porporato ◽  
Jinyu Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Aerobic Glycolysis ◽  
Effector Function ◽  
Glycolytic Flux ◽  
Acid Oxidation ◽  
T Cell Function

Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limited respiratory capacity. Strikingly, blockade of inhibitory receptor PD-1 stimulated the production of IFNγ in chronic T cells, but failed to shift their metabolism towards aerobic glycolysis, as observed in effector T cells. Instead, chronic T cells appeared to rely on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to produce ATP for IFNγ synthesis. Check-point blockade, however, increased mitochondrial production of superoxide and reduced viability and effector function. Thus, in the absence of a glycolytic switch, PD-1-mediated inhibition appears essential for limiting oxidative metabolism linked to effector function in chronic T cells, thereby promoting survival and functional fitness.

scholarly journals Long-term exposure to decabrominated diphenyl ether impairs CD8 T-cell function in adult mice

2014 ◽  
Vol 11 (4) ◽  
pp. 367-376 ◽  
Author(s):  
Weihong Zeng ◽  
Ying Wang ◽  
Zhicui Liu ◽  
Asma Khanniche ◽  
Qingliang Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Diphenyl Ether ◽  
Cd8 T Cell ◽  
Adult Mice ◽  
T Cell Function
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