Possible involvement of regulatory T cell abnormalities and variational usage of TCR repertoire in children with autoimmune neutropenia

Abstract

Autoimmune neutropenia (AIN) in childhood is characterized by chronic neutropenia and positivity for anti-neutrophil antibodies, resulting in the excessive destruction of neutrophils. In this study, we investigated the involvement of regulatory T cells (T_regs ) in the pathogenesis of AIN in childhood. T_regs have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting T_regs , activated T_regs and non-suppressive T_regs . The frequency of activated T_regs (CD4⁺ CD25⁺ FoxP3^high CD45RA^- T cells) as well as that of total T_regs (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 T_regs 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 T_regs was significantly higher than that reported in control subjects. When the preference between T_regs 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 T_regs and the skew of the TCR-Vβ repertoire in CD4⁺ T cells, including T_regs and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.

Keywords: autoimmunity; children; neutropenia; regulatory T cell; repertoire.