Emerging role of stem cell memory‐like T cell in immune thrombocytopenia

Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by autoantibody-mediated platelet destruction. Multiple factors have been implicated in ITP pathogenesis, including T-lymphocyte dysfunctions. Increasing studies have indicated that stem cell memory-like T cell (TSCM) plays an important role in the development of multiple autoimmune diseases. This study aimed to explore the clinical correlation between the TSCM subset and ITP. The percentages of peripheral blood naïve T cells (TNs), TSCMs, central memory T cells (TCMs), effector memory T cells (TEMs) and effector T cells (TEs) among CD4 + and CD8 + T cells in 20 ITP patients before and after treatment were detected using flow cytometry. Our results showed that the percentages of peripheral blood CD4 + and CD8 + T cells in ITP patients were imbalanced. The percentage of CD8 + TSCMs in peripheral blood before treatment in ITP patients was significantly higher than that in healthy controls, whereas the percentages of the other T cell subsets did not exhibit significant differences. Our study further analysed the correlation between the change in the percentage of CD8 + TSCMs and the treatment efficacy. The results showed that the percentage of peripheral blood CD8 + TSCMs in ITP patients after glucocorticoid treatment significantly decreased and the changes of the percentages of CD8 + TSCMs before and after treatment in complete response (CR) and response (R) patients were obvious. Our finding showed that the imbalance of the percentage of CD8 + TSCMs might be involved in the development of ITP and might serve as a novel indicator of efficacy.

Immunotherapeutic Potential of T Memory Stem Cells

“…The genetically modified T SCM can survive in the body for up to 12 years and has good safety and function (140,164). Convincing evidence in mice and humans shows that T SCM cells are an important tool for adoptive immunity in tumor immunotherapy (143,162). On the contrary, it is precisely because of their powerful immune reconstruction ability that they play a double-edged role in human diseases, and they are also potential therapeutic targets for autoimmune diseases and HIV (Figure 5).…”

“…In patients with immune thrombocytopenia (ITP), the ratio of CD4 + and CD8 + T cells in the peripheral blood is unbalanced. The percentage of CD8 + T SCM in peripheral blood of ITP patients was significantly reduced after glucocorticoid treatment, indicating that the imbalance of the ratio of CD8 + T SCM may be involved in the occurrence and development of ITP (162). In addition, the frequency of acquired aplastic anemia (AA) CD8 + T SCM after immunosuppressive treatment was significantly higher than that of healthy controls.…”

T memory stem cells after allogeneic haematopoietic cell transplantation: unique long‐term kinetics and influence of chronic graft‐versus‐host disease

“…Therefore, the higher proportion of TSCMs after CBT could not be associated with occurrence of cGVHD. An increased proportion of CD4 + or CD8 + TSCMs has been observed in patients with autoimmune disease, such as systemic lupus erythematosus (SLE) (Lee et al, 2018), type 1 diabetes (Vignali et al, 2018), aplastic anaemia (Hosokawa et al, 2016) and immune thrombocytopenia (Cao et al, 2019). Cumulatively, these reports suggest that autoreactive TSCMs may possess long-lasting reservoirs to continuously generate autoreactive effector and memory T cells in autoimmune disease.…”

Characteristics of T-cell receptor repertoire of stem cell-like memory CD4+ T cells

“…(2019) , the peripheral proportion of CD4+ Tscm increased in graft-versus-host disease (GVHD) patients compared with no GVHD patients after HSCT. An increased proportion of CD4 + or CD8 + Tscms has also been observed in patients with autoimmune disease ( Jimbo et al., 2019 ), such as systemic lupus erythematosus (SLE) ( Lee et al., 2018 ), type 1 diabetes ( Vignali et al., 2018 ), aplastic anaemia ( Hosokawa et al., 2016 ), immune thrombocytopenia ( Cao et al., 2019 ) and rheumatoid arthritis ( Cianciotti et al., 2020 ). Recently, T-cell immunotherapies based on Tscm have been developed against HIV and cancer ( Flynn & Gorry, 2014 ).…”