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

1.Peyer‘s斑块细胞分泌IL-5和IL-6(1)PP树突状细胞(DC)，尤其是CD11b等树突状细胞(DC)产生的IL-6水平高于SP DC。(2)我们发现初始的CD4T细胞具有很高的分泌IL-6的能力。(3)我们发现从PP细胞分离的IL-2R、CD3^-B220^-Non-T、Non-B细胞能分泌IL-5来应答IL-2。这些IL-2R^细胞不属于已知的产生IL-5的细胞，如T细胞、肥大细胞、NK细胞或嗜酸性粒细胞。结论1.从PP细胞中分离出IL-2R、CD3~-、B220~-细胞，可导致IL-5产生减少。研究了卵清蛋白诱导的卵白蛋白特异性T细胞受体(TCR)转基因小鼠口服耐受CD4T细胞的信号转导途径。在这些T细胞中，(1)TcR-ζ、ZAP-70、LAT的磷酸化受损，(2)钙反应减弱，NFAT核转位减少，(3)ERK和SAPK(MAPK通路)的正常激活，以及(4)IL-2刺激引起的p27、lt；kip1和gt的降解。因此，口服耐受的CD4T细胞的低反应性似乎与两个缺陷有关：TCR诱导的钙途径激活受损，以及通过IL-2R刺激导致的p27^&kip1和gt；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.