CD99-dependent expansion of myeloid-derived suppressor cells and attenuation of graft-versus-host disease |
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Authors: | Hyo Jin Park Dahye Byun An Hi Lee Ju Hyun Kim Young Larn Ban Masatake Araki Kimi Araki Ken-ichi Yamamura Inho Kim Seong Hoe Park Kyeong Cheon Jung |
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Affiliation: | Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea. |
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Abstract: | CD99 is involved in many cellular events, such as the generation of Hodgkin and Reed-Sternberg cells, T cell costimulation, and leukocyte transendothelial migration. However, these studies have been limited to in vitro or in vivo experiments using CD99-deficient cell lines or anti-CD99 antibodies. In the present study, using CD99-deficient mice established by the exchangeable gene trap method, we investigated the physiologic function of murine CD99. In a B6 splenocytes → bm12 graft-versus-host disease model, wild-type cells were minimally lethal, whereas all mice that received CD99-deficient donor cells developed an early and more severe pathology. Graftversus-host disease in these mice was associated with insufficient expansion of myeloid-derived suppressor cells. This was confirmed by experiments illustrating that the injection of wild-type donor cells depleted of Mac-1(+) cells led to an almost identical disease course as the CD99-deficient donor system. Therefore, these results suggest that CD99 plays a crucial role in the attenuation of graft-versus-host disease by regulating the expansion of myeloid-derived suppressor cells. |
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Keywords: | CD99 graft versus host disease myeloid cells |
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