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TCR-Independent and Caspase-Independent Apoptosis of Murine Thymocytes by CD24 Cross-Linking¹

Kyeong Cheon Jung^*, Weon Seo Park, Hae Jung Kim, Eun Young Choi, Myeong-Cherl Kook, Han-Woong Lee and Youngmee Bae^2,

^* Department of Pathology, Hallym University College of Medicine, Chuncheon, Korea; Department of Pathology, Kangwon National University College of Medicine, and Clinical Research Institute, Kangwon National University Hospital, Chuncheon, Korea; Department of Pathology, College of Medicine, and Research Division for Human Life Science, Seoul National University, Seoul, Korea; and Department of Molecular Cell Biology, Samsung Biomedical Research Center, Sungkyunkwan University School of Medicine, Suwon, Korea

CD24, also referred to as the heat-stable Ag, is a T cell differentiation Ag that is highly expressed on both CD4^-CD8^- double negative and CD4⁺CD8⁺ double positive thymocytes. Here, we report that CD24 ligation by a new anti-CD24 Ab, mT-20, induced the apoptosis of both double negative and double positive thymocytes, as well as the Scid.adh thymic lymphoma cell line, in the absence of TCR/CD3 engagement. CD24-mediated apoptosis of mouse thymocytes and its signaling pathway appeared not to be associated with p53, CD95, TNFR, or caspases. Furthermore, we found that cell death was blocked by the addition of scavengers of reactive oxygen species or by Bcl-2 overexpression, implying the role of CD24 signaling in the mitochondrial regulation. In this study, we suggest that CD24 ligation induced the apoptosis of immature thymocytes independently of both caspase and TCR.

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