Cholera toxin induces a transient depletion of CD8+ intraepithelial lymphocytes in the rat small intestine as detected by microarray and immunohistochemistry
Cholera toxin induces a transient depletion of CD8+ intraepithelial lymphocytes in the rat small intestine as detected by microarray and immunohistochemistry
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DOI：
10.1128/iai.73.9.5595-5602.2005
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发表时间：
2005-09-01
影响因子：
3.1
通讯作者：
Holmgren, J
中科院分区：
文献类型：
--
作者：
Flach, CF;Lange, S;Holmgren, J
霍乱毒素（CT）除了在胃内施用后或在霍乱感染期间引起肠分泌过多之外，还影响肠粘膜网络内的多种调节机制，包括T细胞。通过使用微阵列筛选，实时PCR和免疫组化，我们在这里证明了空肠CD 8（+）上皮内淋巴细胞（IEL）在大鼠胃内CT激发后迅速耗尽。这种消耗可能取决于CT诱导的IEL迁移，因为它与上皮中CD 8（+）细胞的进行性减少和固有层中这些细胞（优先在绒毛基底）的瞬时增加有关。在CT激发后6和18 h检测到绒毛CD 8（+）细胞总数显著减少;这可能反映了空肠粘膜的流出。CD 8（+）IEL的动力学表明，在单次CT给药后72小时，CD 8（+）IEL已恢复到正常上皮内位置，达到原始数量。诱导的迁移似乎依赖于CT的酶A亚基，因为山梨醇和CT B亚基的激发都不能模拟CT对CD 8（+）IEL的作用。此外，检测到RNNTES转录物和蛋白质水平均下降，最有可能是CT诱导的CD 8（+）IEL迁移的结果。这些结果表明CT、上皮细胞和IEL之间存在复杂的相互作用，导致肠道稳态紊乱，这可能与灌胃给予CT的强烈免疫调节作用相关。
Cholera toxin (CT), besides causing intestinal hypersecretion after intragastric administration or during cholera infection, affects a multitude of regulatory mechanisms within the gut mucosal network, including T cells. By use of microarray screening, real-time PCR, and immunohistochemistry, we demonstrate here a rapid depletion of jejunal CD8(+) intraepithelial lymphocytes (IEL) in rats after intragastric CT challenge. This depletion may depend on CT-induced migration of IEL, since it was associated with a progressive decrease of CD8(+) cells in the epithelium and a contemporary transient increase of such cells, preferentially at the base of the villi, in the lamina propria. A significant decrease in the total number of villous CD8(+) cells at 6 and 18 h after CT challenge was detected; this possibly reflects an efflux from the jejunal mucosa. The kinetics of the CD8(+) IEL demonstrate the return to normal intraepithelial position at original numbers already 72 h after the single CT dose. The induced migration seems to be dependent on the enzymatic A-subunit of CT, since challenge with neither sorbitol nor CT B-subunit did mimic the effects of CT on CD8(+) IEL. Furthermore, a decrease in the level of both RNNTES transcript and protein was detected, most likely as a consequence of the CT-induced migration of CD8(+) IEL. These results point to a complex interaction between CT, epitheliall cells, and IEL, resulting in a disturbance of the gut homeostasis, which might have relevance for the strong immunomodullatory effects of intragastrically administered CT.