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Murat Tekgüç, James B. Wing, Motonao Osaki, Jia Long, Shimon Sakaguchi
Significance Immunosuppressive Tregs constitutively express CTLA-4, an immune checkpoint receptor. Addressing the role of CTLA-4 in Treg-suppressive function, we show that Treg-expressed CTLA-4, even in the absence of its cytoplasmic portion, promoted the conjugation of Tregs and antigen-presenting cells (APCs), leading to CTLA-4–dependent trogocytosis of CD80/CD86 and concomitant transfer of membrane fragments from APCs to the Treg cell surface. The depletion or blockade of CD80 by trogocytosis or solubilized CTLA-4, respectively, increased free PD-L1 by disrupting cis-CD80/PD-L1 heterodimers on APCs. Thus, Tregs can exert dual suppressive effects through the limitation of CD80/CD86 and up-regulation of free PD-L1 on APCs. Cancer immunotherapy with anti–CTLA-4 and anti–PD-1/PD-L1 blocking antibodies may enhance tumor immunity by hindering this Treg-mediated immune suppression.
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Tekgüç, M., Wing, J. B., Osaki, M., Long, J., & Sakaguchi, S. (2021). Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proceedings of the National Academy of Sciences, 118(30). https://doi.org/10.1073/pnas.2023739118
Tekgüç, Murat, et al. "Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells." Proceedings of the National Academy of Sciences, vol. 118, no. 30, 2021, https://doi.org/10.1073/pnas.2023739118.
Tekgüç, Murat, James B. Wing, Motonao Osaki, Jia Long, and Shimon Sakaguchi. "Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells." Proceedings of the National Academy of Sciences 118, no. 30 (2021). https://doi.org/10.1073/pnas.2023739118.
Tekgüç M., Wing J. B., Osaki M. [и др.] Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells // Proceedings of the National Academy of Sciences. — 2021. — Vol. 118, № 30. — URL: https://doi.org/10.1073/pnas.2023739118
@article{tekguc2021tregexpressed,
title = {{Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells}},
author = {Murat Tekgüç and James B. Wing and Motonao Osaki and Jia Long and Shimon Sakaguchi},
journal = {Proceedings of the National Academy of Sciences},
year = {2021},
volume = {118},
number = {30},
doi = {10.1073/pnas.2023739118},
url = {https://doi.org/10.1073/pnas.2023739118}
}TY - JOUR AU - Tekgüç, Murat AU - Wing, James B. AU - Osaki, Motonao AU - Long, Jia AU - Sakaguchi, Shimon TI - Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells JO - Proceedings of the National Academy of Sciences VL - 118 IS - 30 PY - 2021 DA - 2021/07/23 DO - 10.1073/pnas.2023739118 UR - https://doi.org/10.1073/pnas.2023739118 ER -
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