CD24 on thymic APCs regulates negative selection of myelin antigen-specific T lymphocytes.
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.
Department of Pathology and Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Xuejun
X
Zhang
Jin-Qing
JQ
Liu
Yun
Y
Shi
Hugh H
HH
Reid
Richard L
RL
Boyd
Mazin
M
Khattabi
Hani Y
HY
El-Omrani
Pan
P
Zheng
Yang
Y
Liu
Xue-Feng
XF
Bai
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051927:CD24 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000096927:AIRE Protein
D001324:Autoantigens; D051927:CD24 Antigen; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D000096927:AIRE Protein; C497890:Cd24a protein, mouse; C571327:Mog protein, mouse