Chan Jennifer L, Tang Katherine C, Patel Anoop P, Bonilla Larissa M, Pierobon Nicola, Ponzio Nicholas M, Rameshwar Pranela
Department of Pharmacology and Physiology, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Blood. 2006 Jun 15;107(12):4817-24. doi: 10.1182/blood-2006-01-0057. Epub 2006 Feb 21.
Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasis and occur partly through antigen presentation (antigen-presenting cells [APCs]) within a narrow window. Indeed, we have verified APC functions of MSCs to recall antigens, Candida albicans and Tetanus toxoid. The target cells have been identified to be CD4(+) T cells. APC assays with IFNgamma-knockdown MSCs and with anti-IFNgamma receptor confirmed that MHC-II expression requires autocrine stimulation by IFNgamma. During APC functions, as IFNgamma levels become elevated, there was a concomitant decrease in MHC-II on MSCs. This observation was correlated with flow cytometry studies showing a gradual decrease in MHC-II expression as IFNgamma levels were increased. The reduced levels of MHC-II correlated with losses in their allogeneic potential, as indicated in mixed lymphocyte reaction. In summary, endogenous and low levels of IFNgamma are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNgamma levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.
间充质干细胞（MSCs）大多存在于成人骨髓（BM）的脉管系统周围。它们发挥免疫抑制作用，表达MHC-II，具有吞噬作用，并支持T细胞的细胞毒性。我们推测，MSCs的这些相互矛盾的特性对骨髓稳态很重要，并且部分是通过在一个狭窄窗口期内的抗原呈递（抗原呈递细胞[APC]）来实现的。事实上，我们已经证实了MSCs作为APC回忆抗原（白色念珠菌和破伤风类毒素）的功能。已确定靶细胞为CD4(+) T细胞。用IFNγ敲低的MSCs和抗IFNγ受体进行的APC检测证实，MHC-II的表达需要IFNγ的自分泌刺激。在APC功能过程中，随着IFNγ水平升高，MSCs上的MHC-II随之减少。这一观察结果与流式细胞术研究相关，该研究表明随着IFNγ水平升高，MHC-II表达逐渐降低。MHC-II水平降低与混合淋巴细胞反应中显示的其同种异体潜力丧失相关。总之，MSCs上MHC-II的表达以及APC功能需要内源性和低水平的IFNγ。APC功能在IFNγ水平升高之前的一个狭窄窗口期内发生。该研究对骨髓抗感染和减轻炎症反应具有重要意义。
