CD8αα intestinal intraepithelial lymphocytes derived from two thymic precursors seed the intestine in early life

Ruscher, Roland, Lee, S. Thera, Salgabo, Oscar C., Breed, Elise R., Osum, Sara H., and Hogquist, Kristin (2020) CD8αα intestinal intraepithelial lymphocytes derived from two thymic precursors seed the intestine in early life. Journal of Immunology, 204 (1). e20192336.

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Abstract

TCRαβ CD4 CD8αα intestinal intraepithelial lymphocytes (CD8αα IEL) descend from thymic precursors. To better define this IEL precursor (IELp) population, we analyzed their maturation, localization, and emigration. Using rigorous lineage exclusion criteria, we defined two precursors among DN TCRβ thymocytes: a nascent PD-1 population and a T-bet population that accumulates with age. Both gave rise to intestinal CD8αα IEL upon adoptive transfer. In adult mice, PD-1 cells contained more self-reactive clones, localized to the cortex, and were dominant in S1PR1-dependent thymic egress. Gut homing α4β7 was already expressed by these IELp at a thymic stage. To understand the kinetics of CD8αα IEL seeding the intestine, we performed "timestamp" experiments: We crossed Cd4 with Rosa26 (stop-floxed tdTomato) mice. In these mice, tamoxifen or its metabolite 4-OHT permanently labels every CD4 expressing cell. As TCRαβ T cells (including CD8αα IEL) go through a CD4 CD8 stage during thymic development, a single dose of tamoxifen or 4-OHT will label thymic IEL precursors permanently, so that they can be tracked when seeding the gut. Our results indicate that these cells enter the intestine during a narrow time window in early life and that this influx is almost completely shut down by the age of 3 weeks. These data provide an important foundation for understanding the biology of this abundant population of barrier surface T cells.

Item ID: 63831
Item Type: Article (Research - C1)
ISSN: 1550-6606
Copyright Information: © 2020 Ruscher et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after thepublication date (seehttp://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0International license, as described athttps://creativecommons.org/licenses/by-nc-sa/4.0/).
Funders: National Institute of Health (NIH), USA
Projects and Grants: NIH grant A37 AI39560, NIH grant PO1 AI35296
Date Deposited: 15 Sep 2020 01:57
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 50%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 50%
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