MHC Class I on murine hematopoietic APC selects Type A IEL precursors in the thymus

Lee, S. Thera, Georgiev, Hristo, Breed, Elise R., Ruscher, Roland, and Hogquist, Kristin A. (2021) MHC Class I on murine hematopoietic APC selects Type A IEL precursors in the thymus. European Journal of Immunology, 51 (5). pp. 1080-1088.

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Abstract

TCRαβ+ CD8α+CD8β–intestinal intraepithelial lymphocytes (CD8αα IEL) are gut T cells that maintain barrier surface homeostasis. Most CD8αα IEL are derived from thymic precursors (IELp) through a mechanism referred to as clonal diversion. In this model, self-reactive thymocytes undergo deletion in the presence of CD28 costimulation, but in its absence undergo diversion to the IEL fate. While previous reports showed that IELp were largely β2m dependent, the APC that drive the development of these cells are poorly defined. We found that both CD80 and CD86 restrain IELp development, and conventional DCs play a prominent role. We sought to define a CD80/86 negative, MHCI positive APC that supports the development to the IEL lineage. Chimera studies showed that MHCI needs to be expressed on hematopoietic APC for selection. As thymic hematopoietic APC are heterogeneous in their expression of MHCI and costimulatory molecules, we identified four thymic APC types that were CD80/86neg/low and MHCI+. However, selective depletion of β2m in individual APC suggested functional redundancy. Thus, while hematopoietic APC play a critical role in clonal diversion, no single APC subset is specialized to promote the CD8αα IEL fate.

Item ID: 69079
Item Type: Article (Research - C1)
ISSN: 1521-4141
Keywords: APC; IEL; MHC class I; Thymus
Copyright Information: © 2021 Wiley-VCH GmbH
Date Deposited: 23 Aug 2021 01:16
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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