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Possible involvement of regulatory T cell abnormalities and variational usage of TCR repertoire in children with autoimmune neutropenia
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  • Satoshi Goda,
  • Seiichi Hayakawa,
  • Shuhei Karakawa,
  • Satoshi Okada,
  • Hiroshi Kawaguchi,
  • Masao Kobayashi
Satoshi Goda
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Seiichi Hayakawa
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Shuhei Karakawa
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Satoshi Okada
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Hiroshi Kawaguchi
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Masao Kobayashi
Hiroshima University Faculty of Medicine Graduate School of Biomedical and Health Sciences
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Abstract

Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for antineutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (Tregs) in the pathogenesis of AIN in childhood. Tregs have been classified into three subpopulations based on the expressions of CD45RA and FOXP3: resting Tregs, activated Tregs, and non-suppressive Tregs. The frequency of activated Tregs (CD4+CD25+FOXP3highCD45RA− T cells) as well as that of total Tregs (CD4+CD25+FOXP3+ T cells) in peripheral blood was significantly decreased in patients with AIN. Analysis of the T cell receptor (TCR)-Vβ repertoire of CD4+ T cells revealed skewed usages in patients with AIN compared with that observed in age-matched control subjects. Regarding T cell subsets, the use of four of 24 TCR-Vβ families in Tregs and one in conventional T cells were increased in patients with AIN. The number of patients with AIN who showed skewed usages of TCR-Vβ family in conventional and Tregs was significantly higher than that reported in control subjects. When the preference between Tregs and conventional T cells in each TCR-Vβ family was individually compared, different use was prominently observed in the TCR-Vβ 9 family in patients with AIN. These results suggest that the quantitative abnormalities of Tregs and the skew of the TCR-Vβ repertoire in CD4+ T cells, including Tregs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.

Peer review status:Published

12 Oct 2020Submitted to Clinical & Experimental Immunology
12 Oct 2020Submission Checks Completed
12 Oct 2020Assigned to Editor
14 Oct 2020Reviewer(s) Assigned
04 Nov 2020Review(s) Completed, Editorial Evaluation Pending
04 Nov 2020Editorial Decision: Revise Minor
21 Nov 20201st Revision Received
23 Nov 2020Review(s) Completed, Editorial Evaluation Pending
23 Nov 2020Editorial Decision: Accept
02 Dec 2020Published in Clinical & Experimental Immunology. 10.1111/cei.13559