Journal
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
Volume 86, Issue 4, Pages 221-228Publisher
WILEY
DOI: 10.1111/sji.12586
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Funding
- MD PhD programme of the University of Helsinki
- Emil Aaltonen Foundation
- Jalmari and Rauha Ahokas Foundation
- Finnish Medical Foundation
- Novo Nordisk Foundation
- University of Helsinki
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Mutations in the autoimmune regulator gene disrupt thymic T cell development and negative selection, leading to the recessively inherited polyendocrine autoimmune disease autoimmune polyendocrine syndrome type 1 (APS-1). The patients also have a functional defect in the FOXP3(+) regulatory T cell population, but its origin is unclear. Here, we have used T cell receptor sequencing to analyse the clonal relationship of major CD4(+) T cell subsets in three patients and three healthy controls. The naive regulatory T cells showed little overlap with helper T cell subsets, supporting divergence in the thymus. The activated/memory regulatory T cell subset displayed more sharing with helper T cells, but was mainly recruited from the naive regulatory T cell population. These clonal patterns were very similar in both patients and controls. However, naive regulatory T cells isolated from the patients had a significantly longer T cell receptor complementarity-determining region 3 than any other population, suggesting failure of thymic selection. These data indicate that the peripheral differentiation of regulatory T cells in APS-1 patients is not different from that in healthy controls. Rather, the patients' naive regulatory T cells may have an intrinsic defect imprinted already in the thymus.
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