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

S. Thera Lee, Hristo Georgiev, Elise R. Breed, Roland Ruscher, Kristin A. Hogquist

Research output: Contribution to journalArticlepeer-review

Abstract

TCRαβ+ CD8α+CD8βintestinal 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.

Original languageEnglish (US)
Pages (from-to)1080-1088
Number of pages9
JournalEuropean Journal of Immunology
Volume51
Issue number5
DOIs
StatePublished - May 2021

Bibliographical note

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Keywords

  • APC
  • IEL
  • MHC class I
  • Thymus

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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