Lymph Node Stromal Cell-Intrinsic MHC Class II Expression Promotes MHC Class I-Restricted CD8 T Cell Lineage Conversion to Regulatory CD4 T Cells.
Lymph Node Stromal Cell-Intrinsic MHC Class II Expression Promotes MHC Class I-Restricted CD8 T Cell Lineage Conversion to Regulatory CD4 T Cells.
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DOI：
10.4049/jimmunol.2100396
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发表时间：
2021-09-15
期刊：
影响因子：
--
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Honan AM;Vazquez EN;Chen Z
MHC I类限制性CD 4 + T细胞早已在健康人以及自身免疫性疾病或癌症患者的自然库中发现，但这些细胞的确切起源仍有待充分表征。在小鼠模型中，成熟的外周CD 8 + T细胞具有在肠系膜淋巴结（MLN）中转化为CD 4 + T细胞的潜力。这种转化可以产生独特的MHCI限制性CD 4 + T细胞群，包括称为MHCI限制性CD 4 + Foxp 3 + T（CI-Treg）细胞的Foxp 3+调节性T细胞。在这项研究中，我们研究了促进小鼠中CD 8向CD 4谱系转化和CI-Treg细胞发育的细胞和分子元件。使用过继转移和骨髓嵌合体实验，我们发现CI-Treg细胞的分化是由淋巴结基质细胞（LNSC）内在MHCII表达驱动的，而不是骨髓来源的APC的MHCII的转胞吞作用。谱系转换伴随着Runx 3对ThPOK转录开关。LNSC在体内的新作用的这一发现使我们开发了一种有效的组织培养方法，使用LNSC在体外产生和扩增CI-Treg细胞。在结肠炎小鼠模型中，用LNSC体外扩增的CI-Treg细胞有效地抑制了由致病性CD 4 + T细胞引起的炎性组织损伤。本研究确定了LNSC表达的MHCII在免疫调节中的新作用以及LNSC产生用于治疗应用的免疫调节细胞的新亚群的潜在利用。
MHC class I-restricted CD4+ T cells have long been discovered in the natural repertoire of healthy humans as well as patients with autoimmune diseases or cancer, but the exact origin of these cells remains to be fully characterized. In mouse models, mature peripheral CD8+ T cells have the potential to convert to CD4+ T cells in the mesenteric lymph nodes (MLN). This conversion can produce a unique population of MHCI-restricted CD4+ T cells including Foxp3+ regulatory T cells termed MHCI-restricted CD4+Foxp3+ T (CI-Treg) cells. In this study we examined the cellular and molecular elements which promote CD8-to-CD4 lineage conversion and the development of CI-Treg cells in mice. Using adoptive transfer and bone marrow chimera experiments, we found that the differentiation of CI-Treg cells was driven by lymph node stromal cell (LNSC)-intrinsic MHCII expression as opposed to transcytosis of MHCII from bone marrow-derived APC. The lineage conversion was accompanied by Runx3 versus ThPOK transcriptional switch. This finding of a new role for LNSC in vivo led us to develop an efficient tissue culture method using LNSC to generate and expand CI-Treg cells in vitro. CI-Treg cells expanded in vitro with LNSC effectively suppressed inflammatory tissue damage caused by pathogenic CD4+ T cells in mouse models of colitis. This study identified a novel role of MHCII expressed by LNSC in immune regulation and the potential utilization of LNSC to generate novel subsets of immune regulatory cells for therapeutic applications.
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DOI：
10.1084/jem.20021387
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthlott T;Kassiotis G;Stockinger B
通讯作者：
Stockinger B
影响因子：
64.8
作者：
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影响因子：
7.3
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通讯作者：
Engelhard, Victor H.
DOI：
10.1084/jem.20051409
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen Z;Herman AE;Matos M;Mathis D;Benoist C
通讯作者：
Benoist C
影响因子：
30.5
作者：
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通讯作者：
Turley, Shannon J.