Research ArticleAUTOIMMUNITY

Increased islet antigen–specific regulatory and effector CD4+ T cells in healthy individuals with the type 1 diabetes–protective haplotype

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Science Immunology  14 Feb 2020:
Vol. 5, Issue 44, eaax8767
DOI: 10.1126/sciimmunol.aax8767

Dominant protection against type 1 diabetes

Polymorphic histocompatibility genes in the HLA locus have a strong influence on genetic susceptibility to type 1 diabetes (T1D). Several high-risk HLA haplotypes increase susceptibility to T1D, whereas the DR1501-DQ6 HLA haplotype confers dominant protection. Wen et al. investigated the mechanistic basis for this protective effect by measuring the frequency of CD4+ T cells reactive with epitopes on islet autoantigens in healthy individuals. Individuals with the protective HLA haplotype had a higher frequency of islet antigen–reactive CD4+ T cells than individuals with high-risk or neutral haplotypes. These CD4+ T cells included both regulatory T cells and effector T cells with a propensity to make IL-10. These findings provide deeper insights into how beneficial subsets of self-reactive T cells maintain prophylaxis against autoimmunity.

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