Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia.
Kohei HosokawaPawel MuranskiXingmin FengDanielle M TownsleyBaoying LiuJared KnickelbeinKeyvan KeyvanfarBogdan DumitriuSawa ItoSachiko KajigayaJames G TaylorMariana J KaplanRobert B NussenblattA John BarrettJohn J O'SheaNeal S YoungPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8(+) TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8(+) TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-γ and IL-2 production was significantly increased in various CD8(+) and CD4(+) T cell subsets in AA patients, including CD8(+) and CD4(+) TSCMs. CD8(+) TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4(+) and CD8(+) TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8(+) TSCM subset is a novel biomarker and a potential therapeutic target for AA.
Keyphrases
- systemic lupus erythematosus
- stem cells
- high frequency
- nk cells
- end stage renal disease
- chronic kidney disease
- immune response
- working memory
- risk assessment
- acute myeloid leukemia
- ankylosing spondylitis
- acute lymphoblastic leukemia
- mesenchymal stem cells
- transcranial magnetic stimulation
- climate change
- long non coding rna
- cell therapy
- smoking cessation
- combination therapy
- high speed
- peripheral blood