GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338315/primary200OKOtherMus musculus Homo sapiens Expression profiling by high throughput sequencingOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338315GEOGSEfalseDonor-derived CD8+CD122+ Tregs generated in mixed donor chimeric NOD mice delete autoreactive T cellsThe establishment of mixed hematopoietic chimerism is a promising way to induce immune tolerance for islet replacement therapy and to treat the underlying autoimmunity in Type 1 diabetes (T1D). Mixed chimerism not only promotes effective thymic negative selection of autoreactive cells but also restores regulatory T cell (Treg) function and peripheral tolerance. In the current study, we determined that a novel class of donor-derived CD8+CD44+CD122+ Tregs (d-CD8+CD122+ Tregs) plays a crucial role in controlling autoimmunity in non-obese diabetic (NOD) mice with induced mixed chimerism. Using adoptive T cell transfer experiments, we showed that d-CD8+CD122+ Tregs abrogate autoimmunity by selectively depleting the exogenously injected diabetogenic T cells in Recombination-Activating Gene deficient NOD mice. These d-CD8+CD122+ Tregs from NOD chimeras show upregulation of Helios, Programmed cell death protein 1, perforin, granzyme-B, CD39, Folate receptor 4, and downregulation of proinflammatory markers like Scart1 and Scart2. Using in vitro assays, we show that d-CD8+CD122+ Tregs respond specifically to a Complementarity-Determining Region-3 peptide sequence derived from T cell receptors of islet antigen-specific autoreactive T cells. Thus, mixed chimerism might be a method to revitalize CD8+CD122+ Tregs which are decreased in number and functionality in NOD mice. Similarly, we found that individuals with T1D have a deficiency in CD8+CD122+ Tregs, suggesting a potential loss of regulatory function accompanies disease onset. Revitalizing CD8+CD122+ Tregs may offer a new therapeutic strategy of restoring immune tolerance in autoimmune diabetes.2026/09/30GSE338315GSM9871179GSM9871178GSM9871193GSM9871192GSM9871195GSM9871194GSM9871197GSM9871196GSM9871199GSM9871198GSM9871191GSM9871190GSM9871208GSM9871201GSM9871189GSM9871200GSM9871203GSM9871202GSM9871205GSM9871204GSM9871207GSM9871206GSM9871182GSM9871181GSM9871184GSM9871183GSM9871186GSM9871185GSM9871188GSM9871187GSM98711803428434290338315Mus musculus Homo sapiens