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

在胸腺上皮细胞缺乏MHC表达的情况下,自身反应性CCR7-胸腺细胞的缺失

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

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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