Professor SDBRI San Diego, California, United States
Abstract Text: Type 1 diabetes (T1D) is an inflammatory autoimmune disease resulting in destruction of insulin secreting beta-cells by T cells. Soon after diagnosis, most T1D patients experience a period of partial remission, characterized by reduced insulin requirement, that can last from several weeks to over a year. The mechanism for partial remission is not known. We have identified and validated a novel CD25+CD127+ CD4 T cell population that is present at a higher frequency in T1D patients with long remission compared to those with short or no remission, and in those who maintain beta-cell function. CD25+CD127+ cells are 90-95% memory cells, the majority of which have an anti-inflammatory Th2-type profile. CD25+CD127+ memory Th2 cells are different from CD25- memory Th2 cells (CD25-neg) - they secrete significantly higher levels of Th2 cytokines, and differential gene expression analysis (DGE) of scRNAseq and CITEseq data shows that Th2-associated genes PTGDR2, IL9R, IL2R, IL17RB, IL4R, GATA3, CCR4, IL10RA, as well as PRDM1 (transcriptional repressor of T-bet and IFN-) and GATA3-AS1 (regulator of GATA3 transcription) are significantly upregulated in CD25+CD127+ memory Th2 cells compared to CD25- memory Th2 cells supporting their anti-inflammatory profile. In addition, genes GZMK, IL6ST, IL12RB and IFNG-AS1, (regulates IFN-g expression) are significantly downregulated. Pathway analysis and differences in CD25+CD127+ Th2 cells in T1D compared to healthy will be discussed. These data support the idea that CD25+CD127+ memory Th2 is a unique cell subset mechanistically linked to protecting from T1D progression.
