Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

Killer Cells, Natural*/immunology ; Apoptosis*/immunology ; Lymphocyte Activation*/immunology; Humans ; DNA Damage ; DNA Replication ; CD56 Antigen/metabolism ; Stress, Physiological/immunology ; T-Lymphocytes/immunology ; Cells, Cultured

NK cells are innate immune effectors that kill virally infected or malignant cells. NK cell deficiency (NKD) occurs when NK cell development or function is impaired and variants in MCM4, GINS1, MCM10, and GINS4 result in NKD. Although NK cells are strongly impacted by mutational deficiencies in helicase proteins, the mechanisms underlying this specific susceptibility are poorly understood. In this study, we induced replication stress in activated NK cells or T cells by chemical and genetic methods. We found that the CD56bright subset of NK cells accumulates more DNA damage and replication stress during activation than do CD56dim NK cells or T cells. Aphidicolin treatment increases apoptosis of CD56bright NK cells through increased pan-caspase expression and decreases perforin expression in surviving cells. These findings show that sensitivity to replication stress affects NK cell survival and function and contributes to NKD.
(Copyright © 2024 by The American Association of Immunologists, Inc.)

R01 AI137275 United States AI NIAID NIH HHS; P30 CA013696 United States CA NCI NIH HHS; 1R01GM132604 United States GF NIH HHS; R01AI137275 United States GF NIH HHS

0 (CD56 Antigen)

Date Created: 20240529 Date Completed: 20240617 Latest Revision: 20240716

20240716

10.4049/jimmunol.2300843

38809096