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*

*此作品的通信作者

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號e48097
期刊eLife
8
DOIs
出版狀態Published - 12月 2019

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