Evaluation of the therapeutic potential of bone marrow-derived myeloid suppressor cell (MDSC) adoptive transfer in mouse models of autoimmunity and allograft rejection.
Evaluation of the therapeutic potential of bone marrow-derived myeloid suppressor cell (MDSC) adoptive transfer in mouse models of autoimmunity and allograft rejection.
复制标题
DOI：
10.1371/journal.pone.0100013
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Louvet C
中科院分区：
文献类型：
--
作者：
Drujont L;Carretero-Iglesia L;Bouchet-Delbos L;Beriou G;Merieau E;Hill M;Delneste Y;Cuturi MC;Louvet C
免疫调节细胞的治疗用途代表了用于治疗不受控制的免疫的有希望的方法。在过去的十年中，髓源性抑制细胞（MDSC）已成为肿瘤生长，炎症，移植或自身免疫的背景下，新的关键调控球员。最近，MDSC已成功地产生在体外从幼稚小鼠骨髓细胞或健康的人PBMC使用最小的细胞因子组合。在这项研究中，我们的目的是评估潜在的过继转移这样的细胞，以控制自身和同种异体免疫小鼠。骨髓细胞与GM-CSF和IL-6的培养物一致地产生了大部分CD 11b + Gr 1hi/lo细胞，其在体外表现出对CD 8 + T细胞增殖的强烈抑制。然而，这些细胞的过继转移未能改变抗原特异性CD 8 + T细胞增殖和体内细胞毒性。此外，MDSC不能防止在严格的1型糖尿病模型中自身免疫的发展。相反，在注射胰腺新抗原肽之前加载细胞加速了疾病的发展。相反，在皮肤移植模型中，重复注射MDSC或单次注射LPS激活的MDSC导致同种异体移植物存活的显著延长。MDSC输注对皮肤移植物存活的有益作用矛盾的是，不能通过供体特异性T细胞应答的降低来解释，而是与T细胞和抗原呈递细胞的系统性过度活化相关，特别是在脾脏中。总之，我们的结果表明，体外产生的MDSC具有治疗潜力，但需要额外的体外因素或辅助免疫抑制治疗，以实现安全和更强大的免疫调节过继转移。
Therapeutic use of immunoregulatory cells represents a promising approach for the treatment of uncontrolled immunity. During the last decade, myeloid-derived suppressor cells (MDSC) have emerged as novel key regulatory players in the context of tumor growth, inflammation, transplantation or autoimmunity. Recently, MDSC have been successfully generated in vitro from naive mouse bone marrow cells or healthy human PBMCs using minimal cytokine combinations. In this study, we aimed to evaluate the potential of adoptive transfer of such cells to control auto- and allo-immunity in the mouse. Culture of bone marrow cells with GM-CSF and IL-6 consistently yielded a majority of CD11b+Gr1hi/lo cells exhibiting strong inhibition of CD8+ T cell proliferation in vitro. However, adoptive transfer of these cells failed to alter antigen-specific CD8+ T cell proliferation and cytotoxicity in vivo. Furthermore, MDSC could not prevent the development of autoimmunity in a stringent model of type 1 diabetes. Rather, loading the cells prior to injection with a pancreatic neo-antigen peptide accelerated the development of the disease. Contrastingly, in a model of skin transplantation, repeated injection of MDSC or single injection of LPS-activated MDSC resulted in a significant prolongation of allograft survival. The beneficial effect of MDSC infusions on skin graft survival was paradoxically not explained by a decrease of donor-specific T cell response but associated with a systemic over-activation of T cells and antigen presenting cells, prominently in the spleen. Taken together, our results indicate that in vitro generated MDSC bear therapeutic potential but will require additional in vitro factors or adjunct immunosuppressive treatments to achieve safe and more robust immunomodulation upon adoptive transfer.
登录
查看更多内容
DOI：
10.4049/jimmunol.1101590
发表时间：
2012-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hu C;Du W;Zhang X;Wong FS;Wen L
通讯作者：
Wen L
DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
4.4
作者：
Nefedova, Y;Huang, M;Gabrilovich, D
通讯作者：
Gabrilovich, D
影响因子：
4.4
作者：
Dilek, Nahzli;Poirier, Nicolas;Vanhove, Bernard
通讯作者：
Vanhove, Bernard
影响因子：
20.3
作者：
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.