Document Type

Article

Publication Date

10-2019

DOI

10.1038/s41467-019-12820-3

Publication Title

Nature Communication

Volume

10

Pages

4882 (15 pg.)

Abstract

Thymic central tolerance eliminates most immature T cells with autoreactive T cell receptors (TCR) that recognize self MHC/peptide complexes. Regardless, an unknown number of autoreactive CD4+Foxp3− T cells escape negative selection and in the periphery require continuous suppression by CD4+Foxp3+ regulatory cells (Tregs). Here, we compare immune repertoires of Treg-deficient and Treg-sufficient mice to find Tregs continuously constraining one-third of mature CD4+Foxp3− cells from converting to pathogenic effectors in healthy mice. These dormant pathogenic clones frequently express TCRs activatable by ubiquitous autoantigens presented by class II MHCs on conventional dendritic cells, including selfpeptides that select them in the thymus. Our data thus suggest that identification of most potentially autoreactive CD4+ T cells in the peripheral repertoire is critical to harness or redirect these cells for therapeutic advantage.

Rights

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Original Publication Citation

Cebula, A., Kuczma, M., Szurek, E., Pietrzak, M., Savage, N., Elhefnawy, W. R., . . . Ignatowicz, L. (2019). Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice. Nature Communications, 10(4882). doi:10.1038/s41467-019-12820-3

ORCID

0000-0003-2122-5105 (Kraj)

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