Đặc điểm của các tế bào bạch cầu DNGR-1+ BDCA3+ ở người như là các tương đương khả dĩ của các tế bào tua CD8α+ ở chuột

Journal of Experimental Medicine - Tập 207 Số 6 - Trang 1261-1271 - 2010
Lionel Franz Poulin1,2,3, Mariolina Salio4, Emmanuel Griessinger1,2,5, Fernando Anjos‐Afonso1,2,5, Ligia Craciun6, Ji‐Li Chen4, Anna M. Keller1,2,5, Olivier Joffre1,2,5, Santiago Zelenay1,2,5, Emma Nye1,2,5, Alaín Le Moine6, Florence Faure7, Vincent Donckier6, David Sancho8, Vincenzo Cerundolo4, Dominique Bonnet1,2,5, Caetano Reis e Sousa1,2,5
1Experimental Pathology Laboratories, Cancer Research UK, London Research Institute, London WC2A 3PX, UK 1 , 2 , 3
2Haematopoietic Stem Cell Laboratory 1 , 2 , 3
3Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
4Nuffield Department of Clinical Medicine, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK 4
5Immunobiology Laboratory, Haematopoietic Stem Cell Laboratory, Experimental Pathology Laboratories, Cancer Research UK, London Research Institute, London WC2A 3PX, UK
6Institute for Medical Immunology, Université Libre de Bruxelles, 6041 Gosselies, Belgium 5
7INSERM U932, Paris, France, and Institut Curie, Centre de Recherche, 75248 Paris, France 6
8Department of Vascular Biology and Inflammation, CNIC- Spanish National Centre for Cardiovascular Research “Carlos III”, 28029 Madrid, Spain 7

Tóm tắt

Trong chuột, một tập hợp các tế bào tua (DCs) được biết đến với tên gọi là DCs CD8α+ đã nổi lên như một yếu tố quan trọng trong việc điều chỉnh các phản ứng của tế bào T và là một mục tiêu triển vọng trong các chiến lược tiêm phòng. Tuy nhiên, việc chuyển giao sang các giao thức lâm sàng đã bị cản trở bởi việc không xác định được DCs CD8α+ ở người. Ở đây, chúng tôi mô tả một quần thể các tế bào DCs của người có biểu hiện DNGR-1 (CLEC9A) và mức độ cao của BDCA3, có hình thái và chức năng tương tự như DCs CD8α+ ở chuột. Chúng tôi mô tả sự hiện diện của những tế bào như vậy trong lách của người và chuột được nhân hóa, đồng thời báo cáo về một giao thức để phát triển chúng in vitro. Giống như các DCs CD8α+ ở chuột, các tế bào DNGR-1+ BDCA3hi của người biểu hiện Necl2, CD207, BATF3, IRF8 và TLR3, nhưng không biểu hiện CD11b, IRF4, TLR7, hoặc (khác với các DCs CD8α+) TLR9. Các tế bào DNGR-1+ BDCA3hi phản ứng với poly I:C và các tác nhân kích hoạt TLR8, nhưng không phản ứng với TLR7, và sản xuất interleukin (IL)-12 khi nhận tín hiệu từ hệ miễn dịch bẩm sinh và tín hiệu từ tế bào T. Đáng chú ý, các tế bào DNGR-1+ BDCA3+ từ các văn hóa in vitro có khả năng nội hóa hiệu quả vật liệu từ các tế bào chết và có thể trình diện xuyên qua kháng nguyên ngoại lai cho các tế bào T CD8+ sau khi được điều trị bằng poly I:C. Việc đặc trưng hóa các tế bào DNGR-1+ BDCA3hi của người và khả năng phát triển chúng in vitro mở ra cơ hội khai thác tập hợp này trong liệu pháp miễn dịch.

Từ khóa


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