Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major

Priming by microbial antigens from the intestinal flora determines the ability of CD4+ T cells to rapidly secrete IL-4 in BALB/c mice infected with Leishmania major
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DOI:
10.4049/jimmunol.165.10.5637
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发表时间:
2000-11-15
影响因子:
4.4
通讯作者:
Glaichenhaus, N
Glaichenhaus, N
中科院分区:
医学2区
文献类型:
--
作者:
Julia, V;McSorley, SS;Glaichenhaus, N

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用主要利什曼原虫感染BALB/c小鼠导致IL-4转录物在CD 4(+)T细胞内快速积累,所述T细胞对哺乳动物RACK 1(LACK)Ag的寄生虫利什曼原虫同源物反应。由于记忆/效应细胞比幼稚细胞更快地分泌IL-4,我们试图分析感染前这些淋巴细胞的表型。事实上,在未感染小鼠中,一部分LACK特异性CD 4(+)T细胞表达典型的CD 62配体(低)CD 44(高)CD 45 RB(低)表型。LACK特异性T细胞在肠道相关淋巴组织中被交叉反应性微生物抗原引发,如它们与细菌提取物的反应性和来自BALB/c小鼠肠系膜LN的APC诱导其增殖的能力所证明的。此外,消化道已被净化的小鼠表现出表达记忆/效应表型的LACK特异性T细胞的比例降低,并且没有表现出由L.少校因此,LACK特异性T细胞代表了CD 4(+)T细胞的一个亚群,其已经获得了快速分泌IL-4的能力,这是由于它们被交叉反应性微生物Ag引发的结果。追踪这些细胞的命运可以提供关于在生理和病理情况下细胞介导的对肠道Ag的免疫应答的调节的信息。
Infection of BALB/c mice with Leishmania major results in the rapid accumulation of IL-4 transcripts within CD4(+) T cells that react to the parasite Leishmania homologue of mammalian RACK1 (LACK) Ag, Because memory/effector cells secrete IL-4 more rapidly than naive cells, we sought to analyze the phenotype of these lymphocytes before infection. Indeed, a fraction of LACK-specific CD4(+) T cells expressed a typical CD62 ligand(low)CD44(high)CD45RB(low) phenotype in uninfected mice. LACK-specific T cells were primed in gut-associated lymphoid tissues by cross-reactive microbial Ags as demonstrated by their reactivity with bacterial extracts and by the ability of APCs from the mesenteric LN of BALB/c mice to induce their proliferation. Also, mice in which the digestive tract has been decontaminated exhibited a reduced proportion of LACK-specific T cells expressing a memory/effector phenotype and did not exhibit the early accumulation of IL-4 transcripts induced by L. major. Thus, LACK-specific T cells represent a subset of CD4(+) T cells which have acquired the ability to rapidly secrete IL-4 as the result of their priming by cross-reactive microbial Ags, Tracking the fate of these cells may provide information about the regulation of cell-mediated immune responses to gut Ags in physiological and pathological situations.