دورية أكاديمية
A Cre-driven allele-conditioning line to interrogate CD4 + conventional T cells.
| العنوان: | A Cre-driven allele-conditioning line to interrogate CD4 + conventional T cells. |
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| المؤلفون: | Andrews LP; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA., Vignali KM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA., Szymczak-Workman AL; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA., Burton AR; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Brunazzi EA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA., Ngiow SF; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Harusato A; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Sharpe AH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA., Wherry EJ; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Taniuchi I; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Workman CJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA., Vignali DAA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA. Electronic address: dvignali@pitt.edu. |
| المصدر: | Immunity [Immunity] 2021 Oct 12; Vol. 54 (10), pp. 2209-2217.e6. Date of Electronic Publication: 2021 Sep 21. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 9432918 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4180 (Electronic) Linking ISSN: 10747613 NLM ISO Abbreviation: Immunity Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: Cambridge, Mass. : Cell Press, c1994- |
| مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes/*cytology , Cell Differentiation/*immunology , Cell Lineage/*immunology , Gene Editing/*methods , Integrases/*genetics, Alleles ; Animals ; CD8-Positive T-Lymphocytes/cytology ; Cell Line ; Mice |
| مستخلص: | CD4 + T cells share common developmental pathways with CD8 + T cells, and upon maturation, CD4 + T conventional T (Tconv) cells lack phenotypic markers that distinguish these cells from FoxP3 + T regulatory cells. We developed a tamoxifen-inducible ThPOK CreERT2.hCD2 line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3 Ametrine-FlpO strain, expressing Ametrine and FlpO in Foxp3 + cells. Breeding these mice resulted in a CD4conv iCreERT2-hCD2 line that allows for the specific manipulation of a gene in CD4 + Tconv cells. As FlpO removes the CreERT2-hCD2 cassette, CD4 + Treg cells are spared from Cre activity, which we refer to as allele conditioning. Comparison with an E8I iCreERT2.GFP mouse that enables inducible targeting of CD8 + T cells, and deletion of two inhibitory receptors, PD-1 and LAG-3, in a melanoma model, support the fidelity of these lines. These engineered mouse strains present a resource for the temporal manipulation of genes in CD4 + T cells and CD4 + Tconv cells. Competing Interests: Declaration of interests D.A.A.V. is a cofounder and stockholder in Novasenta, Tizona, Trishula, and Potenza; a stockholder in Oncorus, Werewolf, and Apeximmune; has patents licensed and royalties in Astellas and BMS; is a scientific advisory board member of Tizona, Werewolf, F-Star, Bicara, and Apeximmune; a consultant to Astellas, BMS, Almirall, Incyte, G1 Therapeutics; and has received research funding from BMS, Astellas, and Novasenta. A.H.S. has patents/pending royalties on the PD-1 pathway from Roche and Novartis. A.H.S. is on the advisory boards of Surface Oncology, Elstar, SQZ Biotechnologies, Elpiscience, Selecta, Bicara, and Monopteros; consults for Novartis; and has received research funding from Novartis, Roche, Quark, Merck, and AbbVie that is unrelated to this project. E.J.W. has consulting agreements with and/or is on the scientific advisory boards of Merck, Elstar, Janssen, Related Sciences, Synthekine, and Surface Oncology; is a founder of Surface Oncology and Arsenal Biosciences; and has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. (Copyright © 2021 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | P01 AI108545 United States AI NIAID NIH HHS; R01 CA203689 United States CA NCI NIH HHS; R01 DK089125 United States DK NIDDK NIH HHS; R01 AI144422 United States AI NIAID NIH HHS; R01 AI129893 United States AI NIAID NIH HHS; P01 AI056299 United States AI NIAID NIH HHS; S10 OD011925 United States OD NIH HHS |
| فهرسة مساهمة: | Keywords: CD4; CD8; T cells; Treg; allele-conditioning; gene editing |
| المشرفين على المادة: | EC 2.7.7.- (Cre recombinase) EC 2.7.7.- (Integrases) |
| تواريخ الأحداث: | Date Created: 20210922 Date Completed: 20211109 Latest Revision: 20211109 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.immuni.2021.08.029 |
| PMID: | 34551314 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1097-4180 |
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| DOI: | 10.1016/j.immuni.2021.08.029 |