Nhắm vào P-glycoprotein: Một chiến lược độc đáo để loại bỏ chọn lọc các tế bào T phản ứng miễn dịch

Blood - Tập 100 - Trang 375-382 - 2002
Martin Guimond1, Antonia Balassy1, Mélanie Barrette1, Sylvie Brochu1, Claude Perreault1, Denis Claude Roy1
1From the Division of Hematology-Immunology, Maisonneuve-Rosemont Hospital Research Center, Department of Medicine, Université de Montréal, and Theratechnologies Inc, Montreal, QC, Canada.

Tóm tắt

T lymphocytes được phát hiện mang P-glycoprotein (Pgp) và thể hiện sự điều hòa chức năng vận chuyển của kênh ion này theo trạng thái kích hoạt của tế bào T. Chúng tôi giả thuyết rằng các hóa chất cytotoxic được Pgp đẩy ra có thể được sử dụng để loại bỏ cụ thể các quần thể tế bào T phản ứng miễn dịch. Trong nghiên cứu này, chúng tôi đã đánh giá khả năng của 4,5-dibromorhodamine methyl ester (TH9402), một chất nhạy sáng có cấu trúc tương tự như rhodamine, một loại phẩm màu được Pgp vận chuyển và trở nên cực kỳ độc tế bào khi được kích hoạt bằng ánh sáng nhìn thấy để chọn lọc làm cạn kiệt các tế bào T dị ứng. Việc kích thích các tế bào T bằng mitogens hoặc các tế bào có phức hợp tương thích mô chính khác dòng đã dẫn đến việc giữ lại ưu tiên hợp chất TH9402 từ rhodamine trong các tế bào T đã kích hoạt, cả CD4+ và CD8+. Liệu pháp tế bào quang động của các tế bào T đã tiếp xúc với TH9402 đã dẫn đến việc loại bỏ chọn lọc các quần thể tế bào T phản ứng miễn dịch. Ngoài ra, phương pháp điều trị này bảo tồn các tế bào T đang nghỉ ngơi và khả năng của chúng để đáp ứng với các tế bào bên ngoại. Sự ức chế Pgp đã làm tăng sự giữ lại tế bào của phẩm màu trong các tế bào T chưa kích hoạt và dẫn đến sự thất thoát của chúng sau khi tiếp xúc với ánh sáng. Vì vậy, việc nhắm vào các tế bào thiếu Pgp có thể đại diện cho một chiến lược hấp dẫn cho sự phòng ngừa và điều trị bệnh triệu chứng ghép chống lại chủ và các rối loạn miễn dịch allo hoặc tự miễn khác.

Từ khóa

#P-glycoprotein #T lymphocytes #cytoxicity #immunoreactive T cells #photodynamic therapy

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