Journal article

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

Rushika C Wirasinha, Anna Chan, Jin Yan Yap, Daniel Y Hu, Charis E Teh, Daniel HD Gray, Christopher C Goodnow, Stephen R Daley

CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2019

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-reactiv..

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Grants

Awarded by National Health and Medical Research Council


Awarded by Australia Fellowship


Funding Acknowledgements

We thank Eric Huseby (University of Massachusetts Medical School) for the gift of the Yae62 beta-tg and B3K506 beta-tg mice, Dale Godfrey and Marcin Ciula for the PBS44/CD1d tetramers and the staff of Monash Animal Research Platform, FlowCore and Micromon for technical assistance. This research was supported by the Monash Biomedicine Discovery Institute, by the National Health and Medical Research Council Grant 1107464 to SRD, Grant 1016953 and Australia Fellowship 585490 to CCG.