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CD24 on thymic APCs regulates negative selection of myelin antigen‐specific T lymphocytes
Author(s) -
Zhang Xuejun,
Liu JinQing,
Shi Yun,
Reid Hugh H.,
Boyd Richard L.,
Khattabi Mazin,
ElOmrani Hani Y.,
Zheng Pan,
Liu Yang,
Bai XueFeng
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201142024
Subject(s) - cd24 , biology , myelin oligodendrocyte glycoprotein , immunology , negative selection , antigen , t cell , microbiology and biotechnology , experimental autoimmune encephalomyelitis , gene , genetics , stem cell , immune system , genome , cancer stem cell
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 / ∼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.