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.
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Acknowledgements
We thank Eric Huseby (University of Massachusetts Medical School) for the gift of the Yae62β-tg and B3K506β-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.
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Wirasinha, R.C., Chan, A., Yap, J.Y. et al. Deletion of self-reactive CCR7– thymocytes in the absence of MHC expression on thymic epithelial cells. Cell Death Differ 26, 2727–2739 (2019). https://doi.org/10.1038/s41418-019-0331-8
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DOI: https://doi.org/10.1038/s41418-019-0331-8
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