PD1 blockade improves survival and CD8 + cytotoxic capacity, without increasing inflammation, during normal microbial experience in old mice.

Autor: Dahlquist KJV; Biochemistry, Molecular Biology and Biophysics Graduate Program, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.; Center for Immunology, University of Minnesota, Minneapolis, MN, USA., Huggins MA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA., Yousefzadeh MJ; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.; Department of Medicine, Columbia Center for Translational Immunology, Columbia Center for Healthy Longevity, Columbia University, New York, NY, USA., Soto-Palma C; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA., Cholensky SH; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA., Pierson M; Center for Immunology, University of Minnesota, Minneapolis, MN, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA., Smith DM; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA., Hamilton SE; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.; Center for Immunology, University of Minnesota, Minneapolis, MN, USA.; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA., Camell CD; Biochemistry, Molecular Biology and Biophysics Graduate Program, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA. ccamell@umn.edu.; Department of Biochemistry, Molecular Biology and Biophysics, Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA. ccamell@umn.edu.; Center for Immunology, University of Minnesota, Minneapolis, MN, USA. ccamell@umn.edu.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2024 Jul; Vol. 4 (7), pp. 915-925. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1038/s43587-024-00620-4
Abstrakt: By 2030, individuals 65 years of age or older will make up approximately 20% of the world's population 1 . Older individuals are at the highest risk for mortality from infections, largely due to the pro-inflammatory, dysfunctional immune response, which is collectively known as immunosenescence 2 . During aging, CD8 + T cells acquire an exhausted phenotype, including increased expression of inhibitory receptors, such as programmed cell death 1 (PD1), a decline in effector function and elevated expression of inflammatory factors 3-7 . PD1 reduces T cell receptor activity via SHP2-dependent dephosphorylation of multiple pathways; accordingly, inhibiting PD1 activity through monoclonal antibodies increases CD8 + T cell effector response in young mice 8-11 . Attempts to improve CD8 + T cell responses by blocking inhibitory receptors are attractive; however, they can lead to adverse immune events due to overamplification of T cell receptor signaling and T cell activation 12,13 . Here we investigated the effect of monoclonal anti-PD1 immunotherapy during normal microbial experience, otherwise known as exposure to dirty mice, to determine whether it either improves exhausted CD8 + T cell responses in old mice or leads to a heightened inflammatory response and increased mortality.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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