期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 105, 期 6, 页码 1947-1956出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgaa130
关键词
PD-1; PD-L1; partial remission phase; type 1 diabetes; T cell subsets
资金
- National Key R&D Program of China [2017YFC1309604, 2016YFC1305000]
- Science and Technology Major Project of Hunan Province [2017SK1020]
- Natural Science Foundation of Hunan Province, China [2019JJ40419]
Context: Partial remission (PR) in type 1 diabetes (T1D) is accompanied by downregulation of the immune response. Programmed cell death-1 (PD-1) and its ligand (PD-L1) are important immunosuppressive molecules, but their changes in the PR phase are unclear. Objective: We investigated the dynamic changes of PD-1/PD-L1 expression on T cells around the PR phase in T1D. Methods: Ninety-eight T1D patients were recruited cross-sectionally and grouped according to PR status into nonremitters (individuals who did not undergo PR during the disease course; n = 39), pre-PR (n = 15), mid-PR (n = 30), and post-PR (n = 14) subgroups. PR was defined according to C-peptide level >= 300 pmol/L or index of insulin-adjusted hemoglobin A1c <= 9 as recommended. Among all the 98 patients, 29 newly diagnosed individuals were prospectively followed up for 1 year. The dynamic changes of PD-1/PD-L1 expression, frequency of regulatory T cells (Tregs) and IL-35(+) Tregs among peripheral CD4/CD8(+) T cells were determined. Results: PD-1/PD-L1 on CD4(+)/CD8(+) T cells showed a dynamic change around the PR phase: lowest in pre-PR phase, restored in mid-PR phase, and declined again in post-PR phase. Conversely, this pattern did not occur for nonremitters. Notably, PD-1 expression on CD8(+) T cells in mid-PR was positively correlated with the length of the PR phase. The percentages of circulating Tregs and IL-35(+) Tregs showed no relation to PR. Conclusions: The PR phase is associated with restoration of PD-1/PD-L1 on CD4(+) and CD8(+) T cells, suggesting that PD-1/PD-L1 may be a potential target for prolonging this phase in T1D.
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