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

• Published in: The Journal of immunology (1950) Vol. 196; no. 4; pp. 1568 - 1578
• Main Authors: Hosokawa, Kohei, Muranski, Pawel, Feng, Xingmin, Townsley, Danielle M, Liu, Baoying, Knickelbein, Jared, Keyvanfar, Keyvan, Dumitriu, Bogdan, Ito, Sawa, Kajigaya, Sachiko, Taylor, 6th, James G, Kaplan, Mariana J, Nussenblatt, Robert B, Barrett, A John, O'Shea, John, Young, Neal S
• Format: Journal Article
• Language: English
• Published: United States 15.02.2016
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1501739

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.