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

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 T1D. In this study, using Cox model multivariate analysis we validate our previous findings that patients (n = 84) with the highest frequency of CD4+ CD25+CD127hi (127-hi) cells at diagnosis experience the longest partial remission and we show that the 127-hi cell population is a mix of Th1- and Th2-type cells with a significant bias towards anti-inflammatory Th2-type cells. In addition, we extend these findings to show that patients with the highest frequency of 127-hi cells at diagnosis are significantly more likely to maintain beta-cell function. Moreover, in patients treated with Alefacept in the TIDAL clinical trial, the probability of responding favorably to the anti-inflammatory 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 anti-inflammatory environment that is permissive for partial remission, beta-cell survival and response to anti-inflammatory immunotherapy.