Functional characterization of CD4(+) T cells in aplastic anemia

Shahram Kordasti; Judith Marsh; Sufyan Al-Khan; Jie Jiang; Alexander Smith; Azim Mohamedali; Pilar Perez Abellan; Caroline Veen; Benedetta Costantini; Austin G. Kulasekararaj; Nana Benson-Quarm; Thomas Seidl; Syed A. Mian; Farzin Farzaneh; Ghulam J. Mufti

doi:10.1182/blood-2011-08-368308

Functional characterization of CD4(+) T cells in aplastic anemia

Shahram Kordasti, Judith Marsh, Sufyan Al-Khan, Jie Jiang, Alexander Smith, Azim Mohamedali, Pilar Perez Abellan, Caroline Veen, Benedetta Costantini, Austin G. Kulasekararaj, Nana Benson-Quarm, Thomas Seidl, Syed A. Mian, Farzin Farzaneh, Ghulam J. Mufti

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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 nonsevere AA (P = .01). Th17 cells were in-creased in severeAA(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.

Original language	English
Pages (from-to)	2033 - 2043
Number of pages	11
Journal	Blood
Volume	119
Issue number	9
DOIs	https://doi.org/10.1182/blood-2011-08-368308
Publication status	Published - 1 Mar 2012

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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 nonsevere AA (P = .01). Th17 cells were in-creased in severeAA(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.",

author = "Shahram Kordasti and Judith Marsh and Sufyan Al-Khan and Jie Jiang and Alexander Smith and Azim Mohamedali and Abellan, {Pilar Perez} and Caroline Veen and Benedetta Costantini and Kulasekararaj, {Austin G.} and Nana Benson-Quarm and Thomas Seidl and Mian, {Syed A.} and Farzin Farzaneh and Mufti, {Ghulam J.}",

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doi = "10.1182/blood-2011-08-368308",

language = "English",

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T1 - Functional characterization of CD4(+) T cells in aplastic anemia

AU - Kordasti, Shahram

AU - Marsh, Judith

AU - Al-Khan, Sufyan

AU - Jiang, Jie

AU - Smith, Alexander

AU - Mohamedali, Azim

AU - Abellan, Pilar Perez

AU - Veen, Caroline

AU - Costantini, Benedetta

AU - Kulasekararaj, Austin G.

AU - Benson-Quarm, Nana

AU - Seidl, Thomas

AU - Mian, Syed A.

AU - Farzaneh, Farzin

AU - Mufti, Ghulam J.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - 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 nonsevere AA (P = .01). Th17 cells were in-creased in severeAA(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.

AB - 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 nonsevere AA (P = .01). Th17 cells were in-creased in severeAA(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.

U2 - 10.1182/blood-2011-08-368308

DO - 10.1182/blood-2011-08-368308

M3 - Article

SN - 1528-0020

VL - 119

SP - 2033

EP - 2043

JO - Blood

JF - Blood

IS - 9

ER -

Functional characterization of CD4(+) T cells in aplastic anemia

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