Rasmusson Ida, Uhlin Michael, Le Blanc Katarina, Levitsky Victor
Division of Clinical Immunology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
J Leukoc Biol. 2007 Oct;82(4):887-93. doi: 10.1189/jlb.0307140. Epub 2007 Jul 3.
Mesenchymal stem cells (MSCs), isolated from adult human bone marrow, have immunomodulatory properties. The functional outcomes of MSCs-CTL interactions remain poorly characterized. In this study, we demonstrate that MSCs remain resistant to CTL lysis, even after pulsing with the specific synthetic peptide at high concentrations, in spite of surface expression of the relevant MHC class I allele. MSCs were also much less sensitive to lysis by an allo-specific CTL clone as compared with HLA-matched lymphoblastoid cell lines. MSCs induced CD25 up-regulation, albeit at relatively low levels, and were unable to induce CD3 or CD8 down-regulation at the surface of CTLs. MSCs also failed to induce IFN-gamma and TNF-alpha production by the CTLs. Furthermore, peptide-pulsed MSCs were inefficient in stimulating tyrosine phosphorylation in specific CTLs. Our results demonstrate that MSCs induce only an abortive activation program in fully differentiated, effector CTLs, which does not involve activation of major CTL effector functions. These data may have important implications for the development of therapeutic strategies based on administration of in vitro-expanded MSCs.
从成人骨髓中分离出的间充质干细胞（MSCs）具有免疫调节特性。MSCs与细胞毒性T淋巴细胞（CTL）相互作用的功能结果仍未得到充分表征。在本研究中，我们证明，尽管相关的I类主要组织相容性复合体（MHC）等位基因在表面表达，但即使在高浓度下用特定合成肽脉冲处理后，MSCs仍对CTL裂解具有抗性。与HLA匹配的淋巴母细胞系相比，MSCs对同种异体特异性CTL克隆的裂解也不太敏感。MSCs诱导CD25上调，尽管水平相对较低，并且无法在CTL表面诱导CD3或CD8下调。MSCs也未能诱导CTL产生γ干扰素（IFN-γ）和肿瘤坏死因子-α（TNF-α）。此外，肽脉冲处理的MSCs在刺激特定CTL中的酪氨酸磷酸化方面效率低下。我们的结果表明，MSCs仅在完全分化的效应CTL中诱导一种流产激活程序，该程序不涉及主要CTL效应功能的激活。这些数据可能对基于体外扩增的MSCs给药的治疗策略的开发具有重要意义。
