학술논문
Generation of an Inhibitory NK Cell Subset by TGF-β1/IL-15 Polarization.
Document Type
Academic Journal
Author
Chung DC; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Garcia-Batres CR; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Millar DG; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Wong SWY; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Elford AR; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Mathews JA; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.; Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.; Wang BX; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Nguyen LT; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Shaw PA; Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Clarke BA; Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Bernardini MQ; Division of Gynecologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.; Sacher AG; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.; Crome SQ; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.; Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.; Ohashi PS; Department of Immunology, University of Toronto, Toronto, ON, Canada.; Tumour Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Source
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
Subject
Language
English
Abstract
NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-β1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-β1 could also induce immunosuppressive NK-like cells. First, we found that TGF-β1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-β-dependent manner. Interestingly, TGF-β1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-β1-rich environments.
(Copyright © 2024 by The American Association of Immunologists, Inc.)
(Copyright © 2024 by The American Association of Immunologists, Inc.)