Wild-type and interleukin-10-deficient regulatory T cells reduce effector T-cell-mediated gastroduodenitis in Rag2-/- mice, but only wild-type regulatory T cells suppress Helicobacter pylori gastritis
Wild-type and interleukin-10-deficient regulatory T cells reduce effector T-cell-mediated gastroduodenitis in Rag2-/- mice, but only wild-type regulatory T cells suppress Helicobacter pylori gastritis
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DOI：
10.1128/iai.01788-06
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Fox, James G.
中科院分区：
文献类型：
--
作者：
Lee, Chung-Wei;Rao, Varada P.;Fox, James G.
CD 4（+）CD 45 RB（hi）CD 25（-）效应T细胞（T.）促进小鼠幽门螺杆菌胃炎，CD 4（+）CD 45 RB（lo）CD 25（+）调节性T细胞（T-R）具有抗炎作用。采用过继转移的方法将H. pylori感染的Rag 2（-/-）小鼠，我们评估了野生型（wt）C57 BL/6或同源白细胞介素-10缺陷型（IL-10（-/-））T-R细胞对胃炎、胃细胞因子和H.幽门定植。感染的Rag 2（-/-）小鼠在105至106 H. pylori CFU/g，无相关胃炎。T细胞转移引起发病，H.与γ干扰素（IFN-γ）和肿瘤坏死因子α表达增加相关的非幽门依赖性泛胃炎和胃炎（胃炎）。T-E细胞转移至H. pylori感染的小鼠导致与炎性细胞因子表达和减少的定殖相关的附加性胃体胃炎。wt T-R细胞降低发病率，H. pylori体胃炎、胃十二指肠炎和炎症细胞因子表达，并逆转了H.幽门螺杆菌定植归因于TE细胞。尽管IL-10-/- TR细胞的效果不如wt TR细胞，但IL-10-/- TR细胞也降低了发病率和胃炎，但不降低H。幽门螺杆菌或胃炎影响T细胞定植抑制。与IL-10-/- TR细胞的接受者相比，来自接受wt TR细胞的小鼠的胃组织表达更高水平的Foxp 3，这与IL-10（-/-）T-R细胞的较低调节活性一致。这些结果表明，野生型T-R细胞抑制T-E细胞介导的H。非幽门依赖性胃炎和H. pylori依赖性胃体炎比IL-10（-/-）T-R细胞更有效。T-E细胞和H. pylori介导的炎症以及wt T-R和IL-10（-/-）T-R细胞之间的调节作用表明，wt T-R细胞的IL-10表达对于胃炎症的调节抑制是重要的。
CD4(+) CD45RB(hi) CD25(-) effector T cells (T.) promote Helicobacter pylori gastritis in mice, and CD4(+) CD45RB(lo) CD25(+) regulatory T cells (T-R) are anti-inflammatory. Using adoptive transfer into H. pylori-infected Rag2(-/-) mice, we evaluated effects of wild-type (wt) C57BL/6 or congenic interleukin-10-deficient (IL-10(-/-)) T-R cells on gastritis, gastric cytokines, and H. pylori colonization. Infected Rag2(-/-) mice colonized in the corpus and antrum with 105 to 106 H. pylori CFU/gram without associated gastritis. T, cell transfer caused morbidity and an H. pylori-independent pangastritis and duodenitis (gastroduodenitis) associated with increased expression of gamma interferon (IFN-gamma) and tumor necrosis factor alpha. T-E cell transfer to H. pylori-infected mice led to additive corpus gastritis associated with inflammatory cytokine expression and reduced colonization. wt T-R cells reduced morbidity, H. pylori corpus gastritis, gastroduodenitis, and inflammatory cytokine expression and reversed the decline in H. pylori colonization attributable to TE cells. Although less effective than wt TR cells, IL-10-/- TR cells also reduced morbidity and gastroduodenitis but did not reduce H. pylori corpus gastritis or impact T, cell inhibition of colonization. Gastric tissues from mice receiving wt TR cells expressed higher levels of Foxp3 compared to recipients of IL-10-/- TR cells, consistent with lower regulatory activity of IL-10(-/-) T-R cells. These results demonstrate that wt T-R cells suppressed T-E-cell-mediated H. pylori-independent gastroduodenitis and H. pylori-dependent corpus gastritis more effectively than IL-10(-/-) T-R cells. Compartmental differences in T-E-cell- and H. pylori-mediated inflammation and in regulatory effects between wt T-R and IL-10(-/-) T-R cells suggest that IL-10 expression by wt T-R cells is important to regulatory suppression of gastric inflammation.