Deletion of self-reactive CCR7- thymocytes in the absence of MHC expression on thymic epithelial cells

Cell Death Differ. 2019 Dec;26(12):2727-2739. doi: 10.1038/s41418-019-0331-8. Epub 2019 Apr 24.

Abstract

The selection of αβ T cells in the thymus is punctuated by checkpoints at which thymocytes differentiate or undergo apoptosis. Wave 1 deletion is defined as apoptosis within nascent αβ T-cell antigen receptor (TCR)-signalled thymocytes that lack CCR7 expression. The antigen-presenting cell (APC) types that mediate wave 1 deletion are unclear. To measure wave 1 deletion, we compared the frequencies of TCRβ + CD5 + Helios + CCR7- cells in nascent thymocyte cohorts in mice with normal or defective apoptosis. This thymocyte population is small in mice lacking major histocompatibility complex (MHC) expression. The scale of wave 1 deletion was increased by transgenic expression of the self-reactive Yae62 TCRβ chain, was almost halved when haemopoietic APCs lacked MHC expression and, surprisingly, was unchanged when epithelial cells lacked MHC expression. These findings demonstrate efficiency, and some redundancy, in the APC types that mediate wave 1 deletion in the normal mouse thymus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, CCR7 / deficiency*
  • Receptors, CCR7 / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*
  • Wiskott-Aldrich Syndrome Protein Family

Substances

  • CCR7 protein, human
  • Ccr7 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, CCR7
  • Wiskott-Aldrich Syndrome Protein Family