CD4+CD25+CD127hi cell frequency predicts disease progression in type 1 diabetes. JCI Insight 2021 Jan 25;6(2)
Date
12/11/2020Pubmed ID
33301420Pubmed Central ID
PMC7934872DOI
10.1172/jci.insight.136114Scopus ID
2-s2.0-85099920283 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Narsale A, Lam B, Moya R, Lu T, Mandelli A, Gotuzzo I, Pessina B, Giamporcaro G, Geoffrey R, Buchanan K, Harris M, Bergot AS, Thomas R, Hessner MJ, Battaglia M, Serti E, Davies JDAuthor
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
CD4-Positive T-Lymphocytes
Child
Child, Preschool
Diabetes Mellitus, Type 1
Disease Progression
Female
Humans
Immunotherapy
Infant
Interleukin-2 Receptor alpha Subunit
Interleukin-7 Receptor alpha Subunit
Male
Multivariate Analysis
Proportional Hazards Models
T-Lymphocyte Subsets
Young Adult
