ELUCIDATION OF THE MOLECULAR MECHANISMS OF THE INTESTINAL IMMUNE RESPONSE TO FOOD PROTEIN ANTIGENS

1.派尔集合淋巴结细胞分泌因特拉肯（IL）-5和IL-6。(1)研究表明，PP树突状细胞（DC），特别是CD 11b ^+ DC，比SP DC产生更高水平的IL-6。(2)我们发现初始CD 4 T细胞具有高的分泌IL-6的能力。(3)我们发现，从PP细胞中分离的IL-2 R ^+ CD 3 ^-B220^-非T、非B细胞对IL-2产生应答，分泌IL-5。这些IL-2 R ^+细胞不属于先前已知的产生IL-5的细胞，如T细胞、肥大细胞、NK细胞或嗜酸性粒细胞。从PP细胞中去除IL-2 R ^+ CD 3 ^-B220^-细胞导致IL-5产生减少。检测了用卵清蛋白喂养的卵清蛋白特异性T细胞受体（TCR）转基因小鼠中诱导的口服耐受性CD 4 T细胞的信号转导途径。在这些T细胞中，证实了（1）TCR-γ、ZAP-70、LAT的磷酸化受损，（2）钙应答受损和NFAT核转位减少，（3）ERK和SAPK（MAPK途径）的正常激活，和（4）<kip1>由IL-2刺激诱导的p27 β的降解受损。因此，口服耐受性CD 4 T细胞中的低反应性似乎与两个缺陷相关：TCR诱导的钙通路活化受损，以及<kip1>通过IL-2 R刺激诱导的p27 β降解受损。

1. Interlaken (IL) -5 and IL-6 secretion of Peyer's patch cells. (1) It was demonstrated that PP dendritic cells (DCs), particularly CD11b^+ DCs produced higher levels of IL-6 compared to SP DCs. (2) We found that naive CD4 T cells had a high capacity to secrete IL-6. (3) We found that IL-2R^+ CD3^-B220^- non T, non-B cells isolated from PP cells secreted IL-5 in response to IL-2. These IL-2R^+ cells did not belong to previously known IL-5 producing cells, such as T cells, mast cells, NK cells or eosinophils. Deoletion of IL-2R^+CD3^-B220^- cells from PP cells resulted in reduced IL-5 production.2. Signal transduction pathways in orally tolerant CD4 T cells induced in ovalbumin-specific T cell receptor (TCR) transgenic mice fed with ovalbumin was examined. In these T cells (1) impaired phosphorylation of TCR-ζ, ZAP-70, LAT (2) impaired calcium responses and decreased NFAT nuclear translocation, (3) normal activation of ERK and SAPK (MAPK pathway), and (4) impaired degradation of p27^<kip1> induced by IL-2 stimulation was demonstrated. Thus, hyporesponsiveness in the orally tolerant CD4 T cell appears to be associated with two defects : impaired TCR-induced activation of the calcium pathway, and impaired p27 ^<kip1> degradation induced by stimulation thorough IL-2R.