Rosinski Steven L, Graves Scott S, Higginbotham Deborah A, Storb Rainer
a Division of Clinical Research, Fred Hutchinson Cancer Research Center , Seattle , WA , USA.
b Department of Medicine , University of Washington , Seattle , WA , USA.
Chimerism. 2015 Oct 2;6(4):54-64. doi: 10.1080/19381956.2016.1270483.
This study tested whether an alloimmune response can occur in the marrow donor when infused or injected with leukocytes from their mixed chimeric transplant recipient. Two mixed chimeras were produced after conditioning with three Gray total body irradiation, donor marrow infusion, and post-grafting immunosuppression. The marrow donors were then repeatedly infused and injected with leukocytes from their respective chimeric recipient. A donor lymphocyte infusion (DLI) into their mixed chimeras had no effect, even after the experiments were repeated. The presence of blood dendritic cells (DCs) of recipient origin was confirmed in chimeric recipients, as well as the presence of microchimerism in the marrow donors. Donor sensitization did occur following placement of a recipient skin graft that was confirmed following DLI into recipients that changed the mixed chimeras into full donor chimeras. These observations suggest that mixed chimerism renders recipient peripheral blood DCs incapable of inducing a donor T cell response.
本研究检测了骨髓供体在输注或注射来自其混合嵌合移植受者的白细胞后,是否会发生同种免疫反应。在进行三次全身照射、供体骨髓输注和移植后免疫抑制预处理后,产生了两名混合嵌合体。然后,骨髓供体被反复输注和注射来自其各自嵌合受体的白细胞。即使在重复实验后,向其混合嵌合体输注供体淋巴细胞(DLI)也没有效果。在嵌合受体中证实存在受体来源的血液树突状细胞(DC),以及在骨髓供体中存在微嵌合体。在将受体皮肤移植给混合嵌合体后,供体确实发生了致敏,在将混合嵌合体转变为完全供体嵌合体的受体中进行DLI后得到了证实。这些观察结果表明,混合嵌合状态使受体外周血DC无法诱导供体T细胞反应。