Measuring Thymic Clonal Deletion at the Population Level.

Autor:	Breed ER; Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455; and., Watanabe M; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892., Hogquist KA; Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455; and hogqu001@umn.edu.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jun 01; Vol. 202 (11), pp. 3226-3233. Date of Electronic Publication: 2019 Apr 22.
DOI:	10.4049/jimmunol.1900191
Abstrakt:	Clonal deletion of T cells specific for self-antigens in the thymus has been widely studied, primarily by approaches that focus on a single receptor (using TCR transgenes) or a single specificity (using peptide-MHC tetramers). However, less is known about clonal deletion at the population level. In this article, we report an assay that measures cleaved caspase 3 to define clonal deletion at the population level. This assay distinguishes clonal deletion from apoptotic events caused by neglect and approximates the anatomic site of deletion using CCR7. This approach showed that 78% of clonal deletion events occur in the cortex in mice. Medullary deletion events were detected at both the semimature and mature stages, although mature events were associated with failed regulatory T cell induction. Using this assay, we showed that bone marrow-derived APC drive approximately half of deletion events at both stages. We also found that both cortical and medullary deletion rely heavily on CD28 costimulation. These findings demonstrate a useful strategy for studying clonal deletion within the polyclonal repertoire. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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