Name: in vivo augmentation of gut-homing regulatory t cell induction
Uploaded: 2020-01-22T13:00:00
Description: Watch this Scientific Journal Video about In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction at JoVE.com

这项工作得到了负责卫生事务的助理国防部长办公室的支持，该计划通过"同行评审医学研究计划"获得第1号奖。W81XWH-15-1-0240 （XT）。意见、解释、结论和建议是作者的意见、解释、结论和建议，不一定得到国防部的认可。这项工作还部分得到了洛马琳达大学医学系的研究创新赠款（681207-2967[XT和GG]、681205-2967[XT]和325491[DJB]的支持。

所有体内动物研究协议都经过洛马琳达大学机构动物护理和使用委员会（IACUC）以及美国陆军医学研究与物资司令部动物护理和使用审查办公室（ACURO）的审查和批准。国防部
1. 制备同时表达1-羟基酶和RALDH2（拉比-CYP-ALDH病毒）的Lenti病毒
<ol><li>第0天：在清晨，在CM-10-D细胞培养基中制备5 x 105细胞/mL的293T细胞。</li>
	<li>种子 20 mL/板在 150 毫米 x 25 毫米培养皿。在37°C和...

<ol>
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在本文中，我们将描述DC-CYP-ALDH细胞的使用，用于增强周围淋巴组织内肠道细胞的诱导。我们的数据表明，DC-CYP-ALDH细胞可以在存在相应基质（即分别为25[OH]D和视黄醇）的情况下，在体外合成1，25（OH）2 D和RA的局部高浓度。由于在有30、31缺症的患者中，分别可以通过维生素D和A补充轻松获得足够的血液浓度，因此，当存在25（OH）D和视黄醇的正?...

炎症性肠病 （IBD） 是胃肠道 （GUT） 中的炎症性慢性疾病。在美国，大约有140万IBD患者。人们普遍认为，对肠道细菌的免疫反应失调会引发疾病，并破坏粘膜上皮屏障1，2。因此，目前美国食品和药物管理局（FDA）批准的药物可以抑制炎症中介的作用，或阻止免疫细胞进入肠道。然而，被攻击的炎症介质和免疫细胞也是免疫防御所必需的。因此，炎症中介抑制剂损害全身免疫防御和免疫细胞阻滞剂削弱肠道免疫防御，两者都可能导致严重后果3，4。此外，免疫细胞阻滞剂还可以阻止调节性T（Treg）细胞进入肠道，从而恶化IBD患者已经受损的肠道免疫耐受性。此外，由于Treg细胞在血液中的积累5，阻断Treg细胞进入肠道也可能导致全身免疫抑制。最后，抑制剂和阻滞剂在瞬时作用下发挥作用，因此需要频繁的管理。频繁使用这些抑制剂和阻滞剂可能会进一步加剧不良的副作用。
最近，我们提出了一个新的策略，可以潜在地减轻甚至消除与当前药物IBD治疗6相关的副作用。这种策略增加了周围淋巴组织6的肠道细胞的诱导。这种策略的原理是，肠道细胞专门归于肠道，因此不会损害全身免疫防御。此外，由于Treg细胞可能形成记忆7，8，肠道细胞可能提供一个稳定的控制慢性肠道炎症在IBD患者，因此，治疗不应该经常进行。此外，由于这种策略增强了体内肠道培养Treg细胞的诱导，因此在高度促进炎的环境中，它与体外产生的Treg细胞的收养转移有关，它不存在体内不稳定的问题。在这方面，体外产生的Treg细胞是治疗自身免疫性疾病11、12、13和移植排斥14、15的拟议策略之一。最后，在此策略中，树突状细胞 （DC） 被设计成产生局部高浓度的两种分子：活性维生素 D（1，25-二羟基维生素 D 或 1，25[OH]2D）和活性维生素 A（视黄酸或 RA）。我们选择了1，25（OH）2 D和RA，因为1，25（OH）2 D可以诱导调节分子的表达（例如，叉头盒P3[foxp3]和白细胞介素-10[IL-10]）16，17，并且RA可以刺激T细胞18的肠道宿主受体的表达。因为1，25（OH）2D和RA也可以容忍DC28，29，我们有理由认为，工程DC将稳定地维持在体内的耐原状态，从而规避与体外产生的耐性DC（TolDC）19、20、21相关的体内不稳定问题。在这方面，TolDCs也是建议在体内增强Treg细胞功能19，20，21的策略之一。为了支持我们的推理，我们已经表明，工程的DC，在体内分娩时，可以增强周围淋巴组织6的肠道胃肠道Treg细胞的诱导。
我们提议的战略的另一个优点是 1，25（OH）2D 还具有其他功能，可能有益于 IBD 患者。这些其他功能包括1，25（OH）2 D的能力，刺激抗菌素22的分泌和抑制致癌23。感染和癌症经常与IBD24，25相关。
为了生成能够产生本地高浓度的1，25（OH）2 D和RA denovo的DC，我们使用慢病毒载体来设计DC，以过度表达两个基因。一个基因是细胞色素P450家族27亚家族B成员1（CYP27B1），编码25-羟基维生素D1+羟基酶（1+-羟基酶），这在生理上催化1，25（OH）2 D的合成。另一个基因是甲醛脱氢酶1家族成员A2（ALDH1a2），编码视网膜醛脱氢酶2（RALDH2），这在生理上催化RA6的合成。
由于在体内扩增肠道Treg细胞诱导在IBD的治疗中可能很重要，在以下协议中，我们将详细说明1+-羟基酶-RALDH2过度表达DC（DC-CYP-ALDH细胞）的生成程序，可用于将来对体内肠道细胞的考察。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>10 mL syringes</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 03-377-23</td>
			<td></td>
		</tr>
		<tr>
			<td>100 mm x 20 mm culture dishes</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# CLS430167</td>
			<td></td>
		</tr>
		<tr>
			<td>12-well culture plates</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 07-200-82</td>
			<td></td>
		</tr>
		<tr>
			<td>150 mm x 25 mm culture dishes</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# CLS430559</td>
			<td></td>
		</tr>
		<tr>
			<td>25-hydroxycholecalciferol (25[OH]D)</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# H4014</td>
			<td></td>
		</tr>
		<tr>
			<td>293T cells</td>
			<td>ATCC</td>
			<td>CRL-3216</td>
			<td></td>
		</tr>
		<tr>
			<td>2-mercaptoethanol</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#: 21985023</td>
			<td></td>
		</tr>
		<tr>
			<td>6-well culture plates</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 07-200-83</td>
			<td></td>
		</tr>
		<tr>
			<td>ALDEFLUOR kit</td>
			<td>Stemcell Technologies</td>
			<td>Cat# 01700</td>
			<td></td>
		</tr>
		<tr>
			<td>Anti-CYP27B1</td>
			<td>Abcam</td>
			<td>Cat# ab95047</td>
			<td></td>
		</tr>
		<tr>
			<td>BD FACSAria II</td>
			<td>BD Biosciences</td>
			<td>N/A</td>
			<td></td>
		</tr>
		<tr>
			<td>CaCl2</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# C1016</td>
			<td></td>
		</tr>
		<tr>
			<td>CM-10-D cell culture medium</td>
			<td></td>
			<td></td>
			<td>DMEM medium containing 10% fetal bovine serum (FBS), 100 U/ml penicillin/streptomycin, 0.055 mM 2-mercaptoethanol (2-ME), 1 mM sodium pyruvate, 0.1 mM nonessential amino acid, and 2 mM L-glutamine.</td>
		</tr>
		<tr>
			<td>CM-10-R cell culture medium</td>
			<td></td>
			<td></td>
			<td>RPMI 1640 medium (no glutamine) containing 10% fetal bovine serum (FBS), 100 U/ml penicillin/streptomycin, 0.055 mM 2-mercaptoethanol (2-ME), 1 mM sodium pyruvate, 0.1 mM nonessential amino acid, and 2 mM L-glutamine.</td>
		</tr>
		<tr>
			<td>CM-4-D cell culture medium</td>
			<td></td>
			<td></td>
			<td>DMEM medium containing 4% fetal bovine serum (FBS), 100 U/ml penicillin/streptomycin, 0.055 mM 2-mercaptoethanol (2-ME), 1 mM sodium pyruvate, 0.1 mM nonessential amino acid, and 2 mM L-glutamine.</td>
		</tr>
		<tr>
			<td>Corning bottle-top vacuum filters, 0.22 mM, 500 mL</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# CLS430513</td>
			<td></td>
		</tr>
		<tr>
			<td>Corning bottle-top vacuum filters, 0.45 mM, 500 mL</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# CLS430514</td>
			<td></td>
		</tr>
		<tr>
			<td>Dissecting scissor</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 08-940</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM medium</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 11960044</td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal bovine serum</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 16000044</td>
			<td></td>
		</tr>
		<tr>
			<td>Forceps</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 22-327379</td>
			<td></td>
		</tr>
		<tr>
			<td>Gibco ACK lysing buffer</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# A1049201</td>
			<td></td>
		</tr>
		<tr>
			<td>Glycerol</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# G5516</td>
			<td></td>
		</tr>
		<tr>
			<td>Goat anti-rabbit IgG</td>
			<td>Abcam</td>
			<td>Cat# ab205718</td>
			<td></td>
		</tr>
		<tr>
			<td>HEPES</td>
			<td>Millipore</td>
			<td>Cat# 391340</td>
			<td></td>
		</tr>
		<tr>
			<td>Lenti-CYP-ALDH</td>
			<td>Custom-made</td>
			<td>1.6-kb mouse CYP27B1 and ALDH1a2 cDNAs were amplified by PCR using a plasmid containing the CYP27B1 cDNA and a plasmid containing the ALDH1a2 cDNA respectively (GeneCopoeia). The amplified CYP27B1 cDNA fragment with a 5&#39; KOZAK ribosome entry sequence was cloned into the pRRL-SIN.cPPt.PGKGFP.WPRE lentiviral vector (Addgene). The resulting construct was designated as lenti-CYP-GFP. The amplified ALDH1a2 cDNA fragment was cloned into the lenti-CYP-GFP to replace the GFP and was designated as lenti-CYP-ALDH. This bicistronic plasmid expresses CYP27B1 controlled by SFFV promoter and ALDH1a2 controlled by PGK promoter.</td>
			<td></td>
		</tr>
		<tr>
			<td>L-glutamine</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#25030081</td>
			<td></td>
		</tr>
		<tr>
			<td>Lipopolysaccharide</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# L3755</td>
			<td></td>
		</tr>
		<tr>
			<td>Murine GM-CSF</td>
			<td>Peprotech</td>
			<td>Cat# 315-03</td>
			<td></td>
		</tr>
		<tr>
			<td>Murine IL-4</td>
			<td>Peprotech</td>
			<td>Cat# 214-14</td>
			<td></td>
		</tr>
		<tr>
			<td>Na2HPO4</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# NIST2186II</td>
			<td></td>
		</tr>
		<tr>
			<td>NaCl</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# S9888</td>
			<td></td>
		</tr>
		<tr>
			<td>Needles</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 14-841-02</td>
			<td></td>
		</tr>
		<tr>
			<td>Nonessential Amino Acids</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#: 11140076</td>
			<td></td>
		</tr>
		<tr>
			<td>pCMVR8.74</td>
			<td>Addgene</td>
			<td>Plasmid# 22036</td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin/Streptomycin</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#15140148</td>
			<td></td>
		</tr>
		<tr>
			<td>Phoshate Balanced Solution (PBS)</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#: 20012027</td>
			<td></td>
		</tr>
		<tr>
			<td>PMD2G</td>
			<td>Addgene</td>
			<td>Plasmid# 12259</td>
			<td></td>
		</tr>
		<tr>
			<td>Polypropylene tube, 15 mL</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# AM12500</td>
			<td></td>
		</tr>
		<tr>
			<td>Polypropylene tube, 50 mL</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# AM12502</td>
			<td></td>
		</tr>
		<tr>
			<td>Protamine sulfate</td>
			<td>Sigma-Aldrich</td>
			<td>Cat# P3369</td>
			<td></td>
		</tr>
		<tr>
			<td>Rabbit polycloncal IgG isotype control</td>
			<td>Abcam</td>
			<td>Cat# ab171870</td>
			<td></td>
		</tr>
		<tr>
			<td>Radioimmunoassay for 1,25(OH)2D measurement</td>
			<td>Heartland Assays</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI 1640 medium, no glutamine</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 21870076</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium pyruvat</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat#: 11360070</td>
			<td></td>
		</tr>
		<tr>
			<td>Sorvall Legend XTR Centrifuge</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 75004521</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile Cell strainers, 40 mm</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# 07-201-430</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile storage bottles, 500 mL</td>
			<td>ThermoFisher Scientific</td>
			<td>Cat# CLS431432</td>
			<td></td>
		</tr>
	</tbody>
</table>

in vivo augmentation of gut-homing regulatory t cell induction

炎症性肠病 （IBD） 是胃肠道 （GUT） 中的炎症性慢性疾病。在美国，大约有140万IBD患者。人们普遍认为，对肠道细菌的免疫反应失调会引发疾病并破坏粘膜上皮屏障。我们最近表明，肠道调节T（Treg）细胞是IBD的一种有前途的治疗方法。因此，本文提出了一种在体内扩增肠道Treg细胞诱导的协议。在此协议中，树突状细胞被设计成产生局部高浓度的两种分子，活性维生素D（1，25-二羟基维生素D或1，25[OH]2D）和活性维生素A（视黄酸或RA）。我们根据先前的发现选择1，25（OH）2 D和RA，表明1，25（OH）2 D可以诱导调节分子的表达（例如，叉头盒P3和白细胞介素-10），RA可以刺激T细胞中肠道宿主受体的表达。为了产生这种工程树突状细胞，我们使用慢病毒载体来转导树突状细胞来过度表达两个基因。一个基因是细胞色素P450家族27亚家族B成员1，编码25-羟基维生素D1+羟基酶，这在生理上催化1，25（OH）2 D的合成。另一个基因是甲醛脱氢酶1家族成员A2，编码视网膜醛脱氢酶2，这在生理上催化RA的合成。该协议可用于今后对体内肠道细胞的考察。

DC-CYP-ALDH细胞表达的1-羟基酶的量显著增加。为了确定BMDC产生的DC-CYP-ALDH细胞是否表示1-羟基酶的含量显著增加，BMDC与慢透-CYP-ALDH病毒一起转导，以产生骨髓衍生的DC-CYP-ALDH细胞（BMDC-CYP-ALDH细胞）。随后，FACS对BMDC-CYP-ALDH细胞的1-羟基酶的表达进行了检查。我们的数据表明，BMDC-CYP-ALDH细胞与亲子细胞相比，显示了1°-羟基酶的增强表达（图1A）。我们还...

Watch this Scientific Journal Video about In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction at JoVE.com

In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction

在这里，我们提出了一个方案，在体内扩增的肠道-细胞调节T细胞诱导。在此协议中，树突状细胞被设计成局部产生高浓度活性维生素D（1，25-二羟基维生素D或1，25[OH]2 D）和活性维生素A（视黄酸或RA）的活性。

在 Vivo 增强的古特-霍姆调节 T 细胞诱导

Inflammatory bowel disease (IBD) is an inflammatory chronic disease in the gastrointestinal tract (GUT). In the United States, there are approximately 1.4 ...

该协议描述了一种潜在的新型治疗策略，可以很容易地修改为人类应用。该技术可直接增强周围淋巴组织中肠道宿主调节T细胞的诱导，即使在高度促进炎症的环境中也可以稳定实施。这些技术还可用于研究活性维生素D和维生素A在周围免疫系统中的作用。此视觉演示将为生成高质量工程树突细胞提供分步说明，这些树突状细胞对于该技术的成功至关重要。首先在150~25毫米培养板的CM-10-D细胞培养基20毫升中，将10倍至7个293T细胞，在37摄氏度和5%的二氧化碳下进行24小时孵育。第二天，加入1.62毫升新鲜准备的双浓缩HBS溶液，9.5微克的包络质粒，17.5微克的包装质粒，和27微克的LENTI-CYP-ALDH质粒到50毫升的康体管。将管内内容物的最终体积与水一起带到 3.0375 毫升，然后滴水添加 202.5 微升的两个摩尔氯化钙。将DNA沉淀混合物在室温下保持20分钟，偶尔混合，然后按293T培养成分滴入3.24毫升溶液，同时轻轻旋转盘子。将盘子放在培养箱中24小时，然后用PBS轻轻清洗每个盘子，用CM-4-D培养培养剂喂养细胞。再培养24小时后，将超级钠收获到无菌瓶中，储存在4至8摄氏度，用新鲜的CM-4-D培养基再喂细胞24小时。第四天，再次收获超级钠，将第三天和第四天的超级钠应变到0.45微米过滤器。然后，通过离心24小时集中VSV-G伪型病毒。第二天，把超级纳特人去。让管子在无菌生物安全柜中的纸巾上排干几分钟，然后将颗粒重新排放在 33.3 微升的无菌 PBS 中，每培养皿含有 5%甘油。对于骨髓衍生的树突状细胞生成，将从BALB/c小鼠收获的头骨和股骨放入含有新鲜培养基的100×20毫米培养皿中。使用解剖剪刀和钳子从骨骼中去除任何组织。当所有骨骼都清洁干净后，使用剪刀切割每块骨头的两端，以暴露骨髓腔。使用装有 30 量针的 10 毫升注射器用 10 毫升新鲜培养培养剂冲洗每根骨骼，在 15 毫升管中采集骨髓。收集所有骨髓后，通过离心沉淀骨髓，将颗粒重新悬浮在两毫升红细胞解液缓冲液中。在室温下4至5分钟后，偶尔摇晃，停止与10毫升细胞培养剂的反应，通过离心收集细胞。将颗粒重新在 CM-10-R 培养基的 10 毫升中，用于计数，并调整细胞的 1 倍至 CM-10-R 培养培养基浓度每毫升 6 个细胞。接下来，每毫升向细胞中加入100个单位的重组喃喃 GM-CSF 和每毫升IL-410个单位。将四毫升细胞板放入六孔培养板的单个孔中，在37摄氏度和5%的二氧化碳下孵育48小时。在孵育结束时，轻轻吸气非粘附细胞。在将细胞返回到细胞培养箱48小时之前，将补充的转基因-CSF和IL-4的新鲜培养剂添加到培养物中。在第二次孵育结束时，将非粘附骨髓衍生的树突状细胞收获到50毫升锥形管中进行离心。为了产生BMDC-CYP-ALDH细胞，每井浓度的CM-10-R培养基每500微升，每500微升的树突状细胞以1倍10至第六树突细胞重新暂停，将500微升细胞板板到新的六井培养板的每个井中。在每个井中加入50微升的LENTI-CYP-ALDH病毒和每毫升蛋白胺8微克，然后将盘子放在培养箱中24小时。第二天，用新鲜培养基代替超级细胞，将盘子返回细胞培养箱24小时。在第二次孵化结束时，每毫升脂质糖可激活100毫微克，在收获前24小时进行功能分析。与亲骨骨髓衍生的树突状细胞相比，BMDC-CYP-ALDH细胞表现出1-α-羟基酶的增强表达。在BMDC-CYP和BMDC-CYP-ALDH细胞培养中，维生素D活性形式的浓度比在亲骨髓衍生树突细胞和BMDC-ALDH细胞培养中观察到的浓度高约20倍。用基质处理的BMDC-CYP-ALDH细胞的荧光强度比用基质处理的亲骨髓衍生树突细胞平均荧光强度高约六倍。这表明BMDC-CYP-ALDH细胞表达显著增强的视网膜去氢酶-2酶活性。DC2.4细胞处理25-羟基维生素D和视网膜不诱导Foxp3阳性CCR9阳性CD4阳性T细胞的丰度显著变化。相比之下，用25-羟基维生素D和视网膜治疗的DC2.4 CYP-ALDH细胞以浓度依赖的方式诱导数量显著增加的肠道调控T细胞。此外，与内向注射控制细胞相比，DC CYP-ALDH细胞在内向BALB/c接受者动物注射后，也诱导foxp3阳性CCR9阳性C24阳性T细胞的数量显著增加。手术的成功取决于健康T细胞和正确制备的DNA混合物的制备。

Research

JoVE Journal

Immunology and Infection

Retroviral Transduction of T-cell Receptors in Mouse T-cells

T细胞受体在小鼠T细胞的逆转录病毒转导

T-cell receptors (TCRs) play a central role in the immune system. TCRs on T-cell surfaces can specifically recognize peptide antigens presented by antigen ...

科研

免疫与感染

Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model

Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model

移植物抗宿主病的诱导和<em在体内</em&gt; T细胞监测中的应用MHC匹配的小鼠模型

Graft-versus-host disease (GVHD) is the limiting barrier to the broad use of bone marrow transplant as a curative therapy for a variety of hematological ...

Generation of Induced Regulatory T Cells from Primary Human Na&iuml;ve and Memory T Cells

Generation of Induced Regulatory T Cells from Primary Human NaÃƒÆ’Ã‚Â¯ve and Memory T Cells

从初级人类的幼稚和记忆T细胞的诱导调节性T细胞的生成

The development and maintenance of immunosuppressive CD4+ regulatory T cells (Tregs) contribute to the peripheral tolerance needed to remain in ...

piggyBac Transposon System Modification of Primary Human T Cells

piggyBac Transposon System Modification of Primary Human T Cells

piggyBac转座子初级人类T细胞系统改造

The piggyBac transposon system is naturally active, originally derived from the cabbage looper moth1,2. This non-viral system is plasmid based, most ...

New Tools to Expand Regulatory T Cells from HIV-1-infected Individuals

新工具展开调节性T细胞的HIV-1感染的个体

CD4+ Regulatory T cells (Tregs) are potent immune modulators and serve an important function in human immune homeostasis. Depletion of Tregs has led to ...

The Use of Fluorescent Target Arrays for Assessment of T Cell Responses In vivo

The Use of Fluorescent Target Arrays for Assessment of T Cell Responses In vivo

荧光目标阵列的T细胞反应评价中的应用<em&gt;在体内</em

The ability to monitor T cell responses in vivo is important for the development of our understanding of the immune response and the design of ...

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices

一个<em&gt;体外</em&gt;急性脑片的少突胶质细胞定向T细胞攻击模式

Death of oligodendrocytes accompanied by destruction of neurons and axons are typical histopathological findings in cortical and subcortical grey matter ...

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

诱导小鼠肠道炎症由效应CD4的过继转移<sup&gt; +</sup&gt; CD45RB<sup&gt;高</sup&gt; T细胞免疫缺陷小鼠

There are many different animal models available for studying the pathogenesis of human inflammatory bowel diseases (IBD), each with its own advantages ...

Mouse Na&#239;ve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Mouse NaÃƒÆ’Ã‚Â¯ve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

鼠标朴素CD4<sup&gt; +</sup&gt; T细胞分离和<em&gt;在体外</em&gt;分化为T细胞亚群

Antigen inexperienced (na&#239;ve) CD4+ T cells undergo expansion and differentiation to effector subsets at the time of T cell receptor (TCR) recognition ...