Dormant pathogenic CD4+ T cells are prevalent in the peripheral repertoire of healthy mice

Anna Cebula, Michal Kuczma, Edyta Szurek, Maciej Pietrzak, Natasha Savage, Wessam R. Elhefnawy, Grzegorz Rempala, Piotr Kraj and Leszek Ignatowicz ()
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Anna Cebula: Georgia State University
Michal Kuczma: Georgia State University
Edyta Szurek: Georgia State University
Maciej Pietrzak: Ohio State University
Natasha Savage: Augusta University
Wessam R. Elhefnawy: Old Dominion University
Grzegorz Rempala: Ohio State University
Piotr Kraj: Old Dominion University
Leszek Ignatowicz: Georgia State University

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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 self-peptides 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.

Date: 2019
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DOI: 10.1038/s41467-019-12820-3

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