PD-1 signaling serves a dual role in suppressing T cell activation but also in protecting from activation-induced cell death
نویسندگان
چکیده
Abstract PD1/PDL1 interactions exert potent inhibitory effects on T cell responses. Inhibition of this pathway results in greater responses and is increasingly used cancer immunotherapy but the long-term PD1 inhibition activation remain unclear. We hypothesized that these gains proliferation cells over time may result loss due to apoptosis via induced death (AICD). investigated using both mouse human models activation. from wild-type or PD1−/− mice were activated vitro by a variety stimuli. observed significantly increased total numbers, as well expression Ki67 CD69 PD-1 −/−T compared controls. However, we identified increase was accompanied at later points. Using vivo adoptive transfer (allogeneic & xenogeneic) which −/−murine cells, given tandem with checkpoint blockade assessed activation, proliferation, apoptosis. early expansion murine −/−cells allogeneic environment Furthermore, transplanted into immunodeficient anti-PD1 also had proliferation. Yet, followed sharper contraction through decreased numbers Annexin V staining. These data suggest regulates means protection, when balance manipulated, experience “short term gain” for “long loss” undergo cost AICD. Supported National Institute Health grant NIH RO1 HL140921 (WJM), CA214048 (WJM).
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.226.11