دورية أكاديمية
PD-1 blockade increases the self-renewal of stem-like CD8 T cells to compensate for their accelerated differentiation into effectors.
| العنوان: | PD-1 blockade increases the self-renewal of stem-like CD8 T cells to compensate for their accelerated differentiation into effectors. |
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| المؤلفون: | Gill AL; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Wang PH; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Lee J; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Hudson WH; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Ando S; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Araki K; Division of Infectious Diseases, Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA., Hu Y; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Wieland A; Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, OH 43210, USA., Im S; Department of Immunology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea., Gavora A; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Medina CB; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Freeman GJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Hashimoto M; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA., Reiner SL; Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA., Ahmed R; Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30329, USA. |
| المصدر: | Science immunology [Sci Immunol] 2023 Aug 04; Vol. 8 (86), pp. eadg0539. Date of Electronic Publication: 2023 Aug 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| مواضيع طبية MeSH: | Programmed Cell Death 1 Receptor* , CD8-Positive T-Lymphocytes*, Humans ; Animals ; Mice ; Antibodies ; Cell Differentiation ; Disease Models, Animal |
| مستخلص: | PD-1 + TCF-1 + stem-like CD8 T cells act as critical resource cells for maintaining T cell immunity in chronic viral infections and cancer. In addition, they provide the proliferative burst of effector CD8 T cells after programmed death protein 1 (PD-1)-directed immunotherapy. However, it is not known whether checkpoint blockade diminishes the number of these stem-like progenitor cells as effector cell differentiation increases. To investigate this, we used the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection. Treatment of chronically infected mice with either αPD-1 or αPD-L1 antibody not only increased effector cell differentiation from the virus-specific stem-like CD8 T cells but also increased their proliferation so their numbers were maintained. The increased self-renewal of LCMV-specific stem-like CD8 T cells was mTOR dependent. We used microscopy to understand the division of these progenitor cells and found that after PD-1 blockade, an individual dividing cell could give rise to a differentiated TCF-1 - daughter cell alongside a self-renewing TCF-1 + sister cell. This asymmetric division helped to preserve the number of stem-like cells. Moreover, we found that the PD-1 + TCF-1 + stem-like CD8 T cells retained their transcriptional program and their in vivo functionality in terms of responding to viral infection and to repeat PD-1 blockade. Together, our results demonstrate that PD-1 blockade does not deplete the stem-like population despite increasing effector differentiation. These findings have implications for PD-1-directed immunotherapy in humans. |
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| معلومات مُعتمدة: | R01 AI139675 United States AI NIAID NIH HHS; P51 OD011132 United States OD NIH HHS; R01 CA279268 United States CA NCI NIH HHS; R01 AI104711 United States AI NIAID NIH HHS; R00 AI153736 United States AI NIAID NIH HHS; P30 CA013696 United States CA NCI NIH HHS; R01 AI030048 United States AI NIAID NIH HHS; R56 AI076458 United States AI NIAID NIH HHS; T32 AI106711 United States AI NIAID NIH HHS; P01 AI056299 United States AI NIAID NIH HHS; GT16001 United States HHMI Howard Hughes Medical Institute |
| المشرفين على المادة: | 0 (Programmed Cell Death 1 Receptor) 0 (Antibodies) |
| تواريخ الأحداث: | Date Created: 20230825 Date Completed: 20230828 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10798572 |
| DOI: | 10.1126/sciimmunol.adg0539 |
| PMID: | 37624909 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2470-9468 |
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| DOI: | 10.1126/sciimmunol.adg0539 |