Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transplantation. 2010 Dec 27;90(12):1307-11. doi: 10.1097/TP.0b013e3181fdd9eb.
Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses.
To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting. The ability to stimulate T-cell responses was then assessed in an allogeneic mixed leukocyte response. Next, we isolated either BALB/c (donor) or C57BL/6 (recipient) KSC-DCs from co-culture and measured the tempo of rejection after cotransplantation with islet grafts in a mouse model of islet transplantation. Finally, we measured the effects of KSC-DC stimulation on B-cell proliferation and IgM/IgG production in allogeneic cultures.
C57BL/6 KSCs induced a BALB/c DC phenotype with significantly decreased MHC class II, increased CD80 expression, and decreased T-cell stimulatory capacity in the mixed leukocyte response (P<0.01 vs. control). Cotransplantation of donor (BALB/c) but not recipient (C57BL/6) KSC-DCs resulted in significant delay of rejection after islet transplantation (P<0.01 vs. control). Finally, stimulation by KSC-DCs resulted in significantly reduced B-cell proliferation and antibody production in allogeneic culture (P<0.01 vs. control).
Our results highlight an important mechanism of MSC-based immunotherapy and its potential for use in clinical transplantation as prevention of rejection and possibly sensitization.
间充质基质细胞（MSCs）是具有免疫调节能力的多能细胞，存在于大多数成人器官中。我们之前证明，在同基因骨髓来源的树突状细胞（DC）培养物中共同培养 C57BL/6 肾脏来源的 MSC（KSCs）会诱导具有降低的主要组织相容性复合物（MHC）II 类/增加的 CD80 表达和抑制 T 细胞反应能力的 DC 表型（KSC-DC）。
为了研究它们对同种异体 DC 的影响，将 C57BL/6 KSCs 添加到初始 BALB/c DC 培养物中，通过荧光激活细胞分选测量 MHC 类 II/CD80 的表面表达。然后在同种异体混合白细胞反应中评估刺激 T 细胞反应的能力。接下来，我们从共培养中分离出 BALB/c（供体）或 C57BL/6（受体）KSC-DC，并在胰岛移植的小鼠模型中测量胰岛移植物共移植后排斥的速度。最后，我们测量 KSC-DC 刺激对同种异体培养中 B 细胞增殖和 IgM/IgG 产生的影响。
C57BL/6 KSCs 诱导 BALB/c DC 表型，其 MHC 类 II 显著降低，CD80 表达增加，混合白细胞反应中的 T 细胞刺激能力降低（P<0.01 与对照相比）。胰岛移植后，共移植供体（BALB/c）而非受体（C57BL/6）KSC-DC 导致排斥明显延迟（P<0.01 与对照相比）。最后，KSC-DC 的刺激导致同种异体培养中 B 细胞增殖和抗体产生明显减少（P<0.01 与对照相比）。
我们的结果强调了基于 MSC 的免疫疗法的重要机制及其在临床移植中的潜在用途，可作为预防排斥和可能的致敏作用。
