title: Functional characterization of CD4+ T cells in aplastic anemia.
abstract: The role of CD4(+) T cells in the pathogenesis of aplastic anemia (AA) is not well characterized. We investigate CD4(+) T-cell subsets in AA. Sixty-three patients with acquired AA were studied. Th1 and Th2 cells were significantly higher in AA patients than in healthy donors (HDs; P = .03 and P = .006). Tregs were significantly lower in patients with severe AA than in HDs (P < .001) and patients with non-severe AA (P = .01). Th17 cells were increased in severe AA (P = .02) but normal in non-severe AA. Activated and resting Tregs were reduced in AA (P = .004; P = .01), whereas cytokine-secreting non-Tregs were increased (P = .003). Tregs from AA patients were unable to suppress normal effector T cells. In contrast, AA effector T cells were suppressible by Tregs from HDs. Th1 clonality in AA, investigated by high-throughput sequencing, was greater than in HDs (P = .03). Our results confirm that Th1 and Th2 cells are expanded and Tregs are functionally abnormal in AA. The clonally restricted expansion of Th1 cells is most likely to be antigen-driven, and induces an inflammatory environment, that exacerbate the functional impairment of Tregs, which are reduced in number.
authors.affiliation: Department of Haematological Medicine, King's College London, Rayne Institute, 123 Coldharbour Lane, London, United Kingdom.
authors.forename: Shahram
authors.initials: S
authors.lastname: Kordasti
authors.forename: Judith
authors.initials: J
authors.lastname: Marsh
authors.forename: Sufyan
authors.initials: S
authors.lastname: Al-Khan
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Alexander
authors.initials: A
authors.lastname: Smith
authors.forename: Azim
authors.initials: A
authors.lastname: Mohamedali
authors.forename: Pilar Perez
authors.initials: PP
authors.lastname: Abellan
authors.forename: Caroline
authors.initials: C
authors.lastname: Veen
authors.forename: Benedetta
authors.initials: B
authors.lastname: Costantini
authors.forename: Austin G
authors.initials: AG
authors.lastname: Kulasekararaj
authors.forename: Nana
authors.initials: N
authors.lastname: Benson-Quarm
authors.forename: Thomas
authors.initials: T
authors.lastname: Seidl
authors.forename: Syed A
authors.initials: SA
authors.lastname: Mian
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzaneh
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D011948:Receptors, Antigen, T-Cell