Walker Jason D, Maier Cheryl L, Pober Jordan S
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 2009 Feb 1;182(3):1548-59. doi: 10.4049/jimmunol.182.3.1548.
Human CMV infection is controlled by T cell-mediated immunity and in immunosuppressed transplant patients it is associated with acute allograft rejection as well as chronic allograft vasculopathy. CMV infects endothelial cells (EC) and it is thought that CMV-specific host immune responses to infected allograft EC contribute to rejection. In vitro, CD4(+) T cells from CMV-positive donors (but not CMV-negative donors) are readily activated by CMV-infected allogeneic EC, although it is unclear how allogeneic CMV-infected EC activate self-class II MHC-restricted memory CD4(+) T cells. In this study, we confirm that purified CD4(+) T cells from CMV(+) donors are activated by allogeneic CMV-infected EC, but find that the response is dependent upon copurified APC expressing class II MHC that are autologous to the T cells. The transfer of CMV Ags from infected EC to APC can be mediated by EC-derived exosome-like particles. These results provide a mechanism by which CMV can exacerbate allograft rejection and suggest a novel function of EC-derived exosomes that could contribute in a more general manner to immune surveillance.
人巨细胞病毒（CMV）感染受T细胞介导的免疫控制，在免疫抑制的移植患者中，它与急性移植物排斥以及慢性移植物血管病变相关。CMV感染内皮细胞（EC），据认为，针对感染的移植物EC的CMV特异性宿主免疫反应会导致排斥反应。在体外，来自CMV阳性供体（而非CMV阴性供体）的CD4(+) T细胞很容易被CMV感染的同种异体EC激活，尽管尚不清楚同种异体CMV感染的EC如何激活自身II类MHC限制性记忆CD4(+) T细胞。在本研究中，我们证实来自CMV(+)供体的纯化CD4(+) T细胞被同种异体CMV感染的EC激活，但发现该反应依赖于与T细胞自体的、共纯化的表达II类MHC的抗原呈递细胞（APC）。CMV抗原从感染的EC转移至APC可由EC衍生的类外泌体颗粒介导。这些结果提供了一种CMV可加剧移植物排斥的机制，并提示EC衍生的外泌体的一种新功能，其可能以更普遍的方式有助于免疫监视。
