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

Abstract

The selection of alphabeta 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 alphabeta 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 TCRbeta + 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 TCRbeta 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.

Type Journal
ISBN 1476-5403 (Electronic) 1350-9047 (Linking)
Authors Wirasinha, R. C.; Chan, A.; Yap, J. Y.; Hu, D. Y.; Teh, C. E.; Gray, D. H. D.; Goodnow, C. C.; Daley, S. R.
Responsible Garvan Author Prof Christopher Goodnow
Publisher Name CELL DEATH AND DIFFERENTIATION
Published Date 2019-12-01
Published Volume 26
Published Issue 12
Published Pages 2727-2739
Status Always Electronic
DOI 10.1038/s41418-019-0331-8
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31019259