Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro
Absence of major histocompatibility complex class I on neural stem cells does not permit natural killer cell killing and prevents recognition by alloreactive cytotoxic T lymphocytes in vitro
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DOI：
10.1634/stemcells.22-6-1101
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Levy, R
中科院分区：
文献类型：
--
作者：
Mammolenti, M;Gajavelli, S;Levy, R
神经干细胞（NSCs）在移植中的潜在应用需要了解肌球蛋白重链（MHC）表达以及T细胞和自然杀伤细胞（NK）识别这一祖细胞群的能力。将13天胚胎（E13） B6 （H-2(b)）小鼠皮质细胞外植培养扩增NSCs。使用抗mhc I/II类单克隆抗体（mab）分析p2 - p17培养的细胞显示这两种产物的边缘表达。虽然暴露于重组小鼠干扰素γ (rmIFNgamma)并没有改变这些干细胞的多电位能力，但mrIFNgamma NSC培养物的滴定表明，在添加3ng /ml rmIFNgamma 60小时后，MHC分子可以被强烈上调。为了评估MHC表达水平低或缺失与高水平的NSCs对细胞毒性T淋巴细胞（CTL）和NK细胞裂解的敏感性，我们检测了未经处理和rmifngamma处理的NSC靶细胞。未处理的NSCs不被BALB/c （H-2(d)）同种异体抗H-2(b) CTL识别，与单抗结果一致；然而，早期和晚期传代的NSCs上MHC产物的上调导致它们被CTL有效裂解。从同基因B6或异基因BALB/c小鼠制备NK细胞。虽然NK细胞能有效杀死对照YAC-1靶细胞，但这些效应物不能杀死mhc缺陷（或表达）的NSC靶细胞。因此，与造血干细胞、胚胎干细胞和间充质干细胞群体相似，未经处理的NSCs不易被T细胞和NK细胞杀死。这些发现表明，移植到同基因或异体受体后，NSCs对宿主T细胞和nk细胞群清除的敏感性可能会降低。
Potential applications of neural stem cells (NSCs) for transplantation requires understanding myosin heavy chain (MHC) expression and the ability of T cells and natural killer (NK) cells to recognize this progenitor population. Cells from the cortices of day-13 embryonic (E13) B6 (H-2(b)) mice were explanted and cultured to expand NSCs. Analysis of P2-P17-cultured cells using anti-MHC class I/II monoclonal antibodies (mAbs) showed marginal expression of both products. Although recombinant murine interferon-gamma (rmIFNgamma) exposure did not alter the multipotential capacity of these stem cells, titration of mrIFNgamma NSC cultures demonstrated that MHC molecules could be strongly upregulated after addition of 3 ng/ml rmIFNgamma for 60 hours. To assess the susceptibility of NSCs with low or absent versus high levels of MHC expression to lysis by cytotoxic T lymphocyte (CTL) and NK populations, untreated and rmIFNgamma-treated NSC target cells were examined. Untreated NSCs were not recognized by BALB/c (H-2(d)) allospecific anti-H-2(b) CTL, consistent with the mAb findings; however, upregulation of MHC products on both early and later passaged NSCs resulted in their efficient lysis by CTL. NK cells were prepared from syngeneic B6 or allogeneic BALB/c mice. Although NK cells effectively killed control YAC-1 target cells, these effectors did not kill MHC-deficient (or expressing) NSC targets. Thus, similar to hematopoietic, embryonic, and mesenchymal stem cell populations, unmanipulated NSCs are not readily killed by T and NK cells. These findings suggest that following transplant into syngeneic or allogeneic recipients, NSCs may exhibit diminished susceptibility to clearance by host T- and NK-cell populations.