IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.
IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.
复制标题
作者：
肠道免疫细胞在宿主防御中很重要，但人们对肠道内人类淋巴系统稳态的决定因素知之甚少。相比之下，淋巴系统的动态平衡在小鼠中已经得到了广泛的研究，在那里已经建立了对功能共同的γ链分子的要求。我们假设，人源化的小鼠如果在具有完整的小鼠共同γ链分子的品系中产生，可以提供对人类肠道淋巴系统动态平衡的洞察。为了解决这一假设，我们使用三个小鼠品系(非肥胖糖尿病(NOD)/严重联合免疫缺陷(SCID)(N/S)、NOD/SCIDγ-Chain−/−(NSG)和RAG2−/−γ-Chain−/−(Dko))和两种人源化技术(骨髓肝胸腺和新生小鼠的人CD34+细胞骨髓移植(HU))产生了四种常见类型的人源化小鼠：N/S-BLT、NSG-BLT、NSG-Hu和DKO-Hu小鼠。在具有完整的共同γ链分子的N/S-BLT小鼠中，观察到在整个小肠和大肠中人类T细胞的水平最高。此外，N/S-BLT小鼠的小肠固有层T细胞群表现出人类肠道特有的表面表型。因此，与其他模型相比，N/S-BLT小鼠广泛的肠道免疫重建在数量和质量上都更好，因此N/S-BLT小鼠非常适合于人类肠道淋巴细胞转运和人类特有疾病影响肠道的分析。
Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common γ-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common γ-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID γ-chain−/− (NSG); and Rag2−/− γ-chain−/− (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34+ cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have an intact common γ-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.
登录
查看更多内容
DOI：
10.1523/jneurosci.5473-10.2011
发表时间：
2011-03-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dash PK;Gorantla S;Gendelman HE;Knibbe J;Casale GP;Makarov E;Epstein AA;Gelbard HA;Boska MD;Poluektova LY
通讯作者：
Poluektova LY
DOI：
10.1097/00042737-199804000-00009
发表时间：
1998-04-01
影响因子：
2.1
作者：
Abuzakouk, M;Carton, J;O'Farrelly, C
通讯作者：
O'Farrelly, C
DOI：
10.1097/00042737-200410000-00003
发表时间：
2004-10-01
影响因子：
2.1
作者：
Carton, J;Byrne, B;O'Farrelly, C
通讯作者：
O'Farrelly, C
DOI：
10.1073/pnas.1101398108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Legrand, Nicolas;Huntington, Nicholas D.;Spits, Hergen
通讯作者：
Spits, Hergen
影响因子：
3.7
作者：
Berges, Bradford K.;Akkina, Sarah R.;Akkina, Ramesh
通讯作者：
Akkina, Ramesh