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

JCI Insight. 2021 Jan 25;6(2):e136114. doi: 10.1172/jci.insight.136114.


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.

Keywords: Autoimmune diseases; Autoimmunity; Diabetes; Immunology; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alefacept / therapeutic use
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / therapy
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy / methods
  • Infant
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-7 Receptor alpha Subunit / blood
  • Male
  • Multivariate Analysis
  • Proportional Hazards Models
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*
  • Young Adult


  • IL2RA protein, human
  • IL7R protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Alefacept