{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE338nnn/GSE338315/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"," Homo sapiens"],"gds_type":[" Expression profiling by high throughput sequencing","Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338315"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Donor-derived CD8+CD122+ Tregs generated in mixed donor chimeric NOD mice delete autoreactive T cells","description":"The 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.","dates":{"publication":"2026/09/30"},"accession":"GSE338315","cross_references":{"GSM":["GSM9871179","GSM9871178","GSM9871193","GSM9871192","GSM9871195","GSM9871194","GSM9871197","GSM9871196","GSM9871199","GSM9871198","GSM9871191","GSM9871190","GSM9871208","GSM9871201","GSM9871189","GSM9871200","GSM9871203","GSM9871202","GSM9871205","GSM9871204","GSM9871207","GSM9871206","GSM9871182","GSM9871181","GSM9871184","GSM9871183","GSM9871186","GSM9871185","GSM9871188","GSM9871187","GSM9871180"],"GPL":["34284","34290"],"GSE":["338315"],"taxon":["Mus musculus"," Homo sapiens"]}}