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

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 ) in the pathogenesis of AIN in childhood. T have been classified into three subpopulations based on the expressions of CD45RA and forkhead box protein 3 (FoxP3): resting T , activated T and non-suppressive T . The frequency of activated T (CD4 CD25 FoxP3 CD45RA T cells) as well as that of total T (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 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 was significantly higher than that reported in control subjects. When the preference between T 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 and the skew of the TCR-Vβ repertoire in CD4 T cells, including T and conventional T cells, may be related to autoantibody production through a human neutrophil antigen-reactive T cell clone.