The frequency of CD4+ and CD8+ circulating T stem cell memory in type 1 diabetes

Abstract

Introduction:The frequencies and functions of T stem cell memory (TSCM) subsets vary in autoimmune diseases. We evaluated the frequencies of CD4 + and CD8 + TSCM subsets as well as their PD-1 expression levels in patients with T1D. Methods: Blood samples were collected from new case (NC) (n = 15), and long-term (LT) (n = 15) groups and healthy controls (n = 15). Five subsets of T cells including TCM(CD4 + /CD8 + CCR7 + CD45RO + CD95 + ), TCM hi (CD4 + / CD8 + CCR7 + CD45RO hi CD95 + ), TEM(CD4 + /CD8 + CCR7 − CD45RO + CD95 + ), TSCM(CD4 + /CD8 + CCR7 + CD45RO − CD95 + ), and T naive (CD4 + / CD8 + CCR7 + CD45RO − CD95 − ) were detected by flow-cytometry. Results:The frequency of CD4 + TSCM was higher in NC patients than LT patients and controls (p < .0001 and p = .0086, respectively). A higher percentage of the CD8 + T naive cells was shown in NC patients as compared with LT and healthy individuals (p = .0003 and p = .0002, respectively). An increased level of PD-1 expression was observed on the CD4 + TCM and TCM hi cells in LT patients as compared with healthy controls (p = .0037 and p = .0145, respectively). Also, the higher PD-1 expression was observed on the CD8 + TCM and TCM hi in NC and LT patients as compared with controls (p = .0068 and p < .0001; p = .0012 and p = .0012, respectively). Conclusion:Considering TSCMs' capacities to generate all memory and effector T cells, our results may suggest a potential association between the increased frequencies of TSCMs and T1D progression.

T memory stem cell characteristics in autoimmune diseases and their promising therapeutic values

“…Since tumor-associated Ags mainly derive from self-Ags, once T SCM cells trigger antitumor responses, it can ultimately cause autoimmune diseases (1, 2, 4). Notably, Hosokawa et al (34) and our team separately showed that T SCM cells are the least exhausted population than other memory T-cell subsets, which may be due to self-renewal potency and possessing high-length telomeres (34,35). This evidence may justify the chronic and progressive hallmarks of autoimmune disorders.…”

“…Notably, Hosokawa et al. ( 34 ) and our team separately showed that T SCM cells are the least exhausted population than other memory T-cell subsets, which may be due to self-renewal potency and possessing high-length telomeres ( 34 , 35 ). This evidence may justify the chronic and progressive hallmarks of autoimmune disorders.…”

A set of circulating microRNAs belonging to the 14q32 chromosomic locus identifies two clinically and phenotypically different subgroups of individuals with recent onset Stage 3 type 1 diabetes

“…Circulating Tscm showed increased frequency in T1DM individuals, thus potentially promoting autoimmunity 74,75 . Hence, their precise role in Cluster B T1DM individuals should be further analysed.…”

“…Overall, Tscm play a crucial role in promoting antitumor and immune reconstitution because of their enhanced stem cell-like self-renewal capacity and can serve as a reservoir of effector T-cells. Circulating Tscm showed increased frequency in T1DM individuals, thus potentially promoting autoimmunity 74,75 . Hence, their precise role in Cluster B T1DM individuals should be further analysed.…”

Different paracrine and cell contact effects of human amniotic fluid-derived mesenchymal stem cells on peripheral blood mononuclear cells of type 1 diabetes patients imply the regulatory role of interferon-γ in their interactions

“…The production of IFNγ by the peripheral immune system of new-onset T1D patients has revealed contradictory outcomes, most of them have reported a Th1-like phenotype with significantly increased levels of CD4 + and CD8 + subpopulations [35][36][37], while some others have recorded significantly lower percentage of peripheral CD4 + and CD8 + cells producing IFNγ compared to healthy individuals [38]. Therefore, it can be concluded that the imbalance of this cytokine, whether lacking/defective or excessive secretion in the microenvironment, plays an important role in the pathogenesis of the disease.…”