Diabetes and other autoimmune endocrine diseases
We have previously shown that the frequency of CD4+ CD25+ CD127hi cells correlate with length of partial remission (LoR) in children with Type 1 Diabetes (T1D). In healthy adults these cells have a strong Th2 bias and a dominant central memory (CM) phenotype. The purpose of this study was to validate the correlation between CD25+ CD127hi cells and LoR in a larger cohort of patients, assess the mechanistic potential for these cells in T1D, and in response to Alefacept in the TIDAL study. In a cohort of 91 T1D patients, a significant correlation is observed between the frequency of CD25+ CD127hi cells at diagnosis and LoR. As previously shown for healthy people, CD25+ CD127hi cells in children with T1D have a Th2 bias, express CD2 and are a mix of CM and effector memory (EM) cells, suggesting that they might be a target for Alefacept. Consistent with this notion, the relative frequency of CD25+ CD127hi cells is significantly lower at all time points post-baseline in Alefacept-treated patients compared to the Placebo group following similar kinetics to that previously reported for CM and EM cells in the TIDAL study. However, the frequency of baseline CD25+ CD127hi cells maintained a positive association with LoR in the Alefacept-treated group, suggesting a role in protection. Possible explanations for the apparent paradox between the capacity of Alefacept to deplete CD25+ CD127hi cells, while maintaining a positive association between CD25+ CD127hi cell frequency and a longer LoR will be discussed.