Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation
Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation
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DOI：
10.1097/01.tp.0000045055.63901.a9
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发表时间：
2003-02-15
期刊：
影响因子：
6.2
通讯作者：
Guinan, EC
中科院分区：
文献类型：
--
作者：
Tse, WT;Pendleton, JD;Guinan, EC
背景。骨髓基质细胞（MSC）可以分化成多种间质组织。为了评估人类 MSC 移植的可行性，我们评估了 MSC 的体外免疫原性及其作为同种抗原呈递细胞 (APC) 的功能。方法。人 MSC 源自与同种异体外周血单核细胞 (PBMC) 的混合细胞培养物并使用。通过流式细胞术分析MSC上免疫调节分子的表达。使用细胞增殖测定和酶联免疫测定分析 MSC 相关抑制活性。结果。尽管抗CD28抗体提供了共刺激信号并且用γ-干扰素对MSC进行了预处理，但当与同种异体PBMC共培养时，MSC未能引发增殖反应。 MSC 在γ-干扰素治疗后组成型表达主要组织相容性复合物 (MHC) I 类和淋巴细胞功能相关抗原 (LFA)-3 抗原以及 MHC II 类和细胞间粘附分子 (ICAM)-1 抗原，但不表达 CD80、CD86 或 CD40 共刺激分子。 MSC 积极抑制由第三方同种异体 PBMC 刺激的应答者 PBMC 以及由抗 CD3 和抗 CD28 抗体刺激的 T 细胞的增殖。通过半透膜分离 MSC 和 PBMC 并没有消除抑制作用。抑制活性不能通过 MSC 产生白细胞介素 10、转化生长因子 β1 或前列腺素 E2 来解释，也不能通过培养基中色氨酸的消耗来解释。结论。人 MSC 无法刺激混合细胞培养物中的同种异体 PBMC 或 T 细胞增殖。与其他非专业 APC 不同，这种功能失败不能通过提供 CD28 介导的共刺激或 γ-干扰素预处理来逆转。相反，MSC 主动抑制 T 细胞增殖，这表明同种异体 MSC 移植可能无需显着的宿主免疫抑制即可完成。
Background. Marrow stromal cells (MSC) can differentiate into multiple mesenchymal tissues. To assess the feasibility of human MSC transplantation, we evaluated the in vitro immunogenicity of MSC and their ability to function as alloantigen presenting cells (APC).Methods. Human MSC were derived and used in mixed cell cultures with allogeneic peripheral blood mononuclear cells (PBMC). Expression of immunoregulatory molecules on MSC was analyzed by flow cytometry. An MSC-associated suppressive activity was analyzed using cell-proliferation assays and enzyme-linked immunoassays.Results. MSC failed to elicit a proliferative response when cocultured with allogeneic PBMC, despite provision of a costimulatory signal delivered by an anti-CD28 antibody and pretreatment of MSC with gamma-interferon. MSC express major histocompatibility complex (MHC) class I and lymphocyte function-associated antigen (LFA)-3 antigens constitutively and MHC class II and intercellular adhesion molecule (ICAM)-1 antigens upon gamma-interferon treatment but do not express CD80, CD86, or CD40 costimulatory molecules. MSC actively suppressed proliferation of responder PBMC stimulated by third-party allogeneic PBMC as well as T cells stimulated by anti-CD3 and anti-CD28 antibodies. Separation of MSC and PBMC by a semipermeable membrane did not abrogate the suppression. The suppressive activity could not be accounted for by MSC production of interleukin-10, transforming growth factor-beta1, or prostaglandin E2, nor by tryptophan depletion of the culture medium.Conclusions. Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures. Unlike other nonprofessional APC, this failure of function is not reversed by provision of CD28-mediated costimulation nor gamma-interferon pretreatment. Rather, MSC actively inhibit T-cell proliferation, suggesting that allogeneic MSC transplantation might be accomplished without the need for significant host immunosuppression.