Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia

J Immunol. 2016 Feb 15;196(4):1568-78. doi: 10.4049/jimmunol.1501739. Epub 2016 Jan 13.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Anemia, Aplastic / blood
  • Anemia, Aplastic / diagnosis
  • Anemia, Aplastic / immunology*
  • Anemia, Aplastic / therapy*
  • Anemia, Sickle Cell / diagnosis
  • Anemia, Sickle Cell / immunology
  • Autoimmune Diseases / immunology
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Precursor Cells, T-Lymphoid / immunology*
  • Recurrence
  • T-Lymphocyte Subsets
  • Treatment Failure
  • Uveitis / diagnosis
  • Uveitis / immunology

Substances

  • Biomarkers
  • Interleukin-2
  • Interferon-gamma