Immunophenotypic Insights into Diabetes Heterogeneity: The Role of CD25-Expressing T-Cells in Ghanaian Type 1 Diabetes Cohorts

Type 1 diabetes (T1D) in sub-Saharan Africa exhibits heterogeneity, characterised by alternative phenotypes that retain C-peptide levels. The T-cell pathology linked to these atypical phenotypes remains largely unexplored. CD25, the interleukin-2 receptor alpha chain, and IL2RA genetic variants are key T-cell factors implicated in T1D immunopathology and may contribute to the heterogeneity of T1D in an African context. This study examined IL2RA genotypes and T-cell phenotypes, both ex vivo and following in vitro stimulation, in Ghanaian individuals diagnosed with T1D and classified into groups of low, mid and high C-peptide levels, alongside healthy controls. Immunophenotyping showed increased CD25 expression on CD4 and CD8 T-cells in the diabetes cohorts, correlating with age, C-peptide and HbA1c. IL2RA genotyping revealed limited variability and no link to CD25 expression. An expansion of CD25/CD127 double-positive conventional T-cells, mainly in naïve and central memory subsets, was observed in T1D with mid and high C-peptide. Following age-matching, the low C-peptide group also demonstrated an increase in CD25/CD127 double-positive T-cells, both ex vivo and after in vitro stimulation. The findings indicate a common pattern of immune dysregulation characterized by the expansion of activated conventional T-cells in T1D with varying C-peptide levels in Ghana.