Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production
Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production
复制标题
DOI：
10.1186/1465-9921-13-25
复制
发表时间：
2012-03-20
影响因子：
5.8
通讯作者：
Wilkes, David S.
中科院分区：
文献类型：
--
作者：
Benson, Heather L.;Suzuki, Hidemi;Wilkes, David S.
背景：供体肺来源的树突状细胞(DC)刺激受体来源的T淋巴细胞，即供体肺来源的树突状细胞(DC)的直接识别被认为是肺移植排斥反应的关键机制。髓样细胞(CDCs)和浆细胞样细胞(PDCs)对T细胞的激活有不同的影响。方法：利用转基因小鼠和抗体去除技术，将供体BALB/c小鼠(H-2(D))移植到C57BL/6小鼠(H-2(B))体内，去除供体BALB/c小鼠(H-2(D))肺组织中的一种或两种细胞类型，然后评估排斥反应的病理变化，以及PDC或CDC诱导的C57BL/6来源的纵隔淋巴结T细胞(CD3+)的增殖和细胞因子的产生。相比之下，接受两种树突状细胞耗尽的移植的小鼠的T细胞没有增殖，这与与所有其他组相比显著降低的急性排斥评分有关。CDCs是干扰素-γ的有效诱导者，而CDCs和pDCs均可诱导IL-10。两种细胞类型对IL-17A的产生有不同的影响。结论：总体来看，供体肺PDCs和CDCs对T细胞增殖和细胞因子产生的直接识别作用不同。去除供体肺CDC和PDC可以预防急性排斥反应的发生。
Background: Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs) stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs) and plasmacytoid (pDCs) are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown.Methods: Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2(d)) prior to transplanting into C57BL/6 mice (H-2(b)), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).Results: Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFN gamma, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.Conclusion: Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.