CD24 on thymic APCs regulates negative selection of myelin antigen-specific T lymphocytes

Xuejun Zhang, Jin-Qing Liu, Yun Shi, Hugh H Reid, Richard L Boyd, Mazin Khattabi, Hani Y El-Omrani, Pan Zheng, Yang Liu, Xue-Feng Bai

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Negative selection plays a key role in the clonal deletion of autoreactive T cells in the thymus. However, negative selection is incomplete; as high numbers of autoreactive T cells can be detected in normal individuals, mechanisms that regulate negative selection must exist. In this regard, we previously reported that CD24, a GPI-anchored glycoprotein, is required for thymic generation of autoreactive T lymphocytes. The CD24-deficient 2D2 TCR transgenic mice (2D2(+) CD24(-/-) ), whose TCR recognizes myelin oligodendrocyte glycoprotein (MOG), fail to generate functional 2D2 T cells. However, it was unclear if CD24 regulated negative selection, and if so, what cellular mechanisms were involved. Here, we show that elimination of MOG or Aire gene expression in 2D2(+) CD24(-/-) mice - through the creation of 2D2(+) CD24(-/-) MOG(-/-) or 2D2(+) CD24(/) approximately Aire(-/-) mice - completely restores thymic cellularity and function of 2D2 T cells. Restoration of CD24 expression on DCs, but not on thymocytes also partially restores 2D2 T-cell generation in 2D2(+) CD24(-/-) mice. Taken together, we propose that CD24 expression on thymic antigen-presenting cells (mTECs, DCs) down-regulates autoantigen-mediated clonal deletion of autoreactive thymocytes.
Original languageEnglish
Pages (from-to)924 - 935
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number4
DOIs
Publication statusPublished - 2012

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