CD5‐expressing CD8⁺ T‐cell subsets differ between children with type 1 diabetes and controls

Abstract

Different lymphocyte subsets are involved in autoimmune pathogenesis of type 1 diabetes (T1D). Previous studies suggested a role of CD5‐expressing T and B cells including rare unconventional lymphocytes with combined T‐ and B‐cell features [dual expressing (DE) cells]. We performed algorithm‐supported multiparameter flow cytometry and quantitative PCR to investigate immune cell subsets and DE cells in children with T1D (n = 20) and matched controls (n = 20). Comparisons of conventional immune cells detected increased proportions of CD3+ T cells in T1D patients, whereas CD19+ B‐cell proportions were comparable to controls. Self‐organizing maps for flow cytometry analyses (FlowSOM) showed highly similar CD5‐expressing B‐cell subsets and no differences for DE cells were detected between the study groups by flow cytometry or specific quantitative PCR. Notably, differences in CD8+ T cells were indicated by FlowSOM and similarity‐based t‐distributed stochastic neighbor embedding (tSNE) analyses. Study group comparisons confirmed significantly reduced CD8+ T‐cell proportions with moderate or low CD5 expression in T1D patients. Finally, in vitro experiments showed stable CD5 expression differences of CD8+ T cells after T‐cell activation, cytokine stimulation and culture. We observed differences of T‐cell coreceptor CD5 expression in T1D patients with potential relevance for immune regulation of CD8+ T‐cell activation.

Thymic self-recognition-mediated TCR signal strength modulates antigen-specific CD8+T cell pathogenicity in non-obese diabetic mice

“…Surprisingly, clinical cases of type 1 diabetes reflect similar findings to our animal mouse model study. Children with T1D exhibit higher CD5 expression in CD8 + T cells compared to healthy controls (63). These observations underscore the complexity of immune responses in autoimmune diseases and warrant further exploration to unravel the underlying mechanisms and hold promise for therapeutic interventions in autoimmune diseases.…”