Intestinal CD8αα IELs derived from two distinct thymic precursors have staggered ontogeny

Ruscher, Roland, Lee, S. Thera, Salgado, Oscar C., Breed, Elise R., Osum, Sara H., and Hogquist, Kristin A. (2020) Intestinal CD8αα IELs derived from two distinct thymic precursors have staggered ontogeny. Journal of Experimental Medicine, 217 (8). e20192336.

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CD8αα intraepithelial lymphocytes (IELs) are abundant T cells that protect the gut epithelium. Their thymic precursors (IELps)include PD-1⁺ type A and Tbet⁺ type B populations, which differ in their antigen-receptor specificities. To better understand CD8αα IEL ontogeny, we performed “time-stamp” fate mapping experiments and observed that it seeds the intestine predominantly during a narrow time window in early life. Adoptively transferred IELps parked better in the intestines of young mice than in adults. In young mice, both type A and type B IELps had an S1PR1⁺ and α4β7⁺ emigration- and mucosal-homing competent phenotype, while this was restricted to type A IELps in adults. Only CD8αα IELs established in early life were enriched in cells bearing type B IELp TCR usage. Together, our results suggest that the young intestine facilitates CD8αα IEL establishment and that early IELs are distinct from IELs established after this initial wave. These data provide novel insight into the ontogeny of CD8αα IELs.

Item ID: 64043
Item Type: Article (Research - C1)
ISSN: 1540-9538
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 the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0International license, as described at
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This article is available Open Access via the publisher's website.

Funders: National Institutes of Health (NIH)
Projects and Grants: NIH grants R37 AI39560 and PO1 AI35296
Date Deposited: 30 Aug 2020 18:52
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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