CD4+CD25+CD127hi cell frequency predicts disease progression in type 1 diabetes

Autor: Aditi Narsale, Breanna Lam, Rosa Moya, TingTing Lu, Alessandra Mandelli, Irene Gotuzzo, Benedetta Pessina, Gianmaria Giamporcaro, Rhonda Geoffrey, Kerry Buchanan, Mark Harris, Anne-Sophie Bergot, Ranjeny Thomas, Martin J. Hessner, Manuela Battaglia, Elisavet Serti, Joanna D. Davies
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: JCI Insight, Vol 6, Iss 2 (2021)
Druh dokumentu: article
ISSN: 2379-3708
DOI: 10.1172/jci.insight.136114
Popis: Transient partial remission, a period of low insulin requirement experienced by most patients soon after diagnosis, has been associated with mechanisms of immune regulation. A better understanding of such natural mechanisms of immune regulation might identify new targets for immunotherapies that reverse type 1 diabetes (T1D). In this study, using Cox model multivariate analysis, we validated our previous findings that patients with the highest frequency of CD4+CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission, and we showed that the 127-hi cell population is a mix of Th1- and Th2-type cells, with a significant bias toward antiinflammatory Th2-type cells. In addition, we extended these findings to show that patients with the highest frequency of 127-hi cells at diagnosis were significantly more likely to maintain β cell function. Moreover, in patients treated with alefacept in the T1DAL clinical trial, the probability of responding favorably to the antiinflammatory drug was significantly higher in those with a higher frequency of 127-hi cells at diagnosis than those with a lower 127-hi cell frequency. These data are consistent with the hypothesis that 127-hi cells maintain an antiinflammatory environment that is permissive for partial remission, β cell survival, and response to antiinflammatory immunotherapy.
Databáze: Directory of Open Access Journals