Mennechet Franck J D, Kasper Lloyd H, Rachinel Nicolas, Minns Laurie A, Luangsay Souphalone, Vandewalle Alain, Buzoni-Gatel Dominique
Department of Microbiology, Dartmouth Medical School, Lebanon, NH, USA.
Eur J Immunol. 2004 Apr;34(4):1059-67. doi: 10.1002/eji.200324416.
Intraepithelial lymphocytes (IEL) play a key role in gut homeostasis and are critical effector cells preventing the inflammatory intestinal lesions induced in mice following oral infection with Toxoplasma gondii. In this intestinal inflammatory model, CD4(+) T lymphocytes from the lamina propria (LP) synergize with the infected enterocytes to secrete pro-inflammatory chemokines and cytokines. In this study, we assessed the mechanisms accounting for the ability of IEL to modulate the inflammatory activity of these cells. Adoptive transfer of IEL purified from wild-type mice, or CD154-,CD95L- or IL-10-deficient mice infected with T. gondii completely impairs the development of the lethal ileitis in recipient mice orally infected with T. gondii. Compared with unprimed IEL isolated from naive mice, the CD8 alpha beta TCR alpha beta subset of primed IEL, isolated from T. gondii-infected mice, secretes increased amount of TGF-beta. IEL interact with the LP CD4(+) T lymphocytes, down-regulate their production of inflammatory cytokines such as IFN-gamma and reduce their proliferative activity. These effects are linked to the secretion of TGF-beta and are correlated with a shift in the balance between Smad7/T-bet down-regulation and Smad2/Smad3 up-regulation in LP CD4(+) T lymphocytes.
上皮内淋巴细胞（IEL）在肠道内环境稳定中起关键作用，是预防小鼠经口感染刚地弓形虫后诱发的肠道炎性病变的关键效应细胞。在这个肠道炎症模型中，固有层（LP）的CD4(+) T淋巴细胞与被感染的肠上皮细胞协同分泌促炎趋化因子和细胞因子。在本研究中，我们评估了IEL调节这些细胞炎性活性能力的机制。从感染刚地弓形虫的野生型小鼠、CD154缺陷型小鼠、CD95L缺陷型小鼠或IL-10缺陷型小鼠中纯化的IEL进行过继转移，完全抑制了经口感染刚地弓形虫的受体小鼠致死性回肠炎的发展。与从未感染小鼠分离的未致敏IEL相比，从感染刚地弓形虫的小鼠分离的致敏IEL的CD8αβ TCRαβ亚群分泌的TGF-β量增加。IEL与LP CD4(+) T淋巴细胞相互作用，下调其炎性细胞因子如IFN-γ的产生，并降低其增殖活性。这些效应与TGF-β的分泌有关，并且与LP CD4(+) T淋巴细胞中Smad7/T-bet下调和Smad2/Smad3上调之间平衡的改变相关。
