A role for phagocytosis in inducing cell death during thymocyte negative selection

Nadia S. Kurd, Lydia K. Lutes, Jaewon Yoon, Shiao Wei Chan, Ivan L. Dzhagalov, Ashley R. Hoover, Ellen A. Robey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Autoreactive thymocytes are eliminated during negative selection in the thymus, a process important for establishing self-tolerance. Thymic phagocytes serve to remove dead thymocytes, but whether they play additional roles during negative selection remains unclear. Here, using a murine thymic slice model in which thymocytes undergo negative selection in situ, we demonstrate that phagocytosis promotes negative selection, and provide evidence for the escape of autoreactive CD8 T cells to the periphery when phagocytosis in the thymus is impaired. We also show that negative selection is more efficient when the phagocyte also presents the negative selecting peptide. Our findings support a model for negative selection in which the death process initiated following strong TCR signaling is facilitated by phagocytosis. Thus, the phagocytic capability of cells that present self-peptides is a key determinant of thymocyte fate.

Original languageEnglish
Article numbere48097
JournaleLife
Volume8
DOIs
StatePublished - Dec 2019

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