Exogenous catalase treatment enhances CD8+ T cell functionality and hinders T cell exhaustion

نویسندگان

چکیده

Abstract ROS are small short-lived oxygen-containing molecules which highly chemically reactive and involved in the regulation of biological processes like T cell activation proliferation. The tumor microenvironment (TME) is a metabolically hostile environment with deficiency nutrients glucose glutamine, accumulation tumor-driven metabolic waste, extreme hypoxia. Hypoxia results impaired mitochondrial function generation excess levels ROS, have been known to promote exhaustion. Here, we investigated how exogenous treatment antioxidant catalase altered CD8+ effector responses exhaustion using OT-I TCR transgenic mice. During differentiation vitro by stimulation cognate antigen followed culture IL-2, addition significantly enhanced differentiation. Catalase-treated cells had higher expression critical markers including CD69 CD25, increased stemness marker TCF-1, secretion cytokines IFNγ TNFα. induction co-culture B16 melanoma expressing ovalbumin (B16-Ova), catalase-treated cytotoxic activity, CD25 lower co-expression PD-1 TIM-3 relative non-treated cells. Our findings uncover new role for altering fate potentially therapeutic tool managing NIH (R01 CA212605)

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)-susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of...

متن کامل

CD8 T cell exhaustion in human visceral leishmaniasis.

Little is known about CD8 T cells in human visceral leishmaniasis (VL) and it is unclear if these cells have a protective, pathological and/or suppressive function. In experimental VL CD8 T cells have been shown to contribute to parasite control and play an important role in vaccine-generated immunity. To better understand the role of CD8 T cells in human VL, we examined molecules associated wi...

متن کامل

T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients.

PURPOSE T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) is a recently identified T-cell coinhibitory receptor. In this study, we aimed to determine the clinical impact of TIGIT in patients with acute myelogenous leukemia (AML) and dissect the role of TIGIT in the pathogenesis of leukemia progression. EXPERIMENTAL DESIGN TIGIT expression on T cell...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.86.11