Brown Kathryn, Sacks Steven H, Wong Wilson
MRC Center for Transplantation, Fifth Floor, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
FASEB J. 2008 Nov;22(11):3776-84. doi: 10.1096/fj.08-107441. Epub 2008 Jul 16.
Intercellular transfer of surface molecules has been demonstrated in vitro, or in vivo under artificial situations. Transplantation is a unique clinical situation in which foreign major histocompatibility complex (MHC) molecules are deliberately introduced. This provides a model to study intercellular MHC transfer because donor MHC molecules can easily be tracked. Here we describe the bidirectional transfer of MHC class II molecules between donor and recipient cells after transplantation of vascularized kidney and cardiac allografts in mice. Cells that are positive for both donor and recipient MHC class II accounted for up to 30% of the donor MHC class II(+) population, suggesting that they play a significant role in the antigen presentation process. The majority of these cells were dendritic cells, but macrophages and B cells were also able to acquire foreign MHC molecules. Most double-positive cells were also positive for costimulatory molecules, indicating a capability to elicit a T-cell response. This transfer of MHC molecules between donor and recipient cells provides a link between the direct and indirect pathways of alloantigen presentation and suggests that MHC transfer is also likely to occur under normal physiological conditions, which has implications in the fields of infection, vaccination, and tumor immunology.
表面分子的细胞间转移已在体外或人工条件下的体内得到证实。移植是一种独特的临床情况,其中会特意引入外来的主要组织相容性复合体(MHC)分子。这提供了一个研究细胞间MHC转移的模型,因为供体MHC分子易于追踪。在此,我们描述了在小鼠血管化肾脏和心脏同种异体移植后,供体和受体细胞之间MHC II类分子的双向转移。供体和受体MHC II类均呈阳性的细胞占供体MHC II类阳性群体的比例高达30%,这表明它们在抗原呈递过程中发挥着重要作用。这些细胞大多数是树突状细胞,但巨噬细胞和B细胞也能够获取外来MHC分子。大多数双阳性细胞的共刺激分子也呈阳性,表明其具有引发T细胞反应的能力。供体和受体细胞之间的这种MHC分子转移在同种异体抗原呈递的直接和间接途径之间建立了联系,并表明MHC转移在正常生理条件下也可能发生,这在感染、疫苗接种和肿瘤免疫学领域具有重要意义。