APPROACHES FOR CONTROLLING INFECTION BY GENE THERAPY

Th2细胞的成功发育需要分化和扩增两个过程，并依赖于IL-4受体(IL-4R)介导的信号的激活水平。在IL-4R下游的信号分子中，STAT6的激活被认为是分化过程中的关键，而IRS-2的磷酸化对细胞增殖是重要的。RAS/MAPK信号通路的激活可能作用于JAK1激酶，增强其活性，改善IL-4R功能。幼稚CD4T细胞中CN的激活诱导JAK3转录上调。在抗TCR激活的幼稚T细胞和已建立的克隆化Th2细胞中，Stat5被发现与IL-4受体复合体具有物理和功能上的相关性。IL-4诱导的STAT5激活似乎在发育中的Th2细胞的扩增过程中起着重要作用。因此，在发育中的Th2细胞中，JAK3和STAT5分子在功能IL-4R复合体中的募集似乎对Th2细胞的发育至关重要。我们证明了与沙门氏菌感染相关的脾肿大是一种宿主防御反应，是由Mac-1^+细胞迁移到感染的脾中引起的。我们试图用编码SV40早期抗原的无辅助子和复制缺陷的重组逆转录病毒来建立小鼠骨髓来源的DC株，并获得了几个可以独立生长的DC株。我们建立了单核细胞增生性李斯特菌突变株，当毒力基因激活时表达ply118基因产物。我们试图利用该突变李斯特菌建立基因转导系统。

Successful development of Th2 cells requires both differentiation and expansion processes, and depends on the activation levels of IL-4 receptor (IL-4R) -mediated signaling. Among signaling molecules downstream of IL-4R, STAT6 activation is thought to be critical for differentiation process, and phosphorylation of IRS-2 is important for proliferation. The activation of Ras/MAPK cascade appears to act on Jak1 kinase to enhance its kinase activity and improve IL-4R function. The activation of CN in naive CD4 T cells induces transcriptional upregulation of Jak3. STAT5 is found to be physically and functionally associated with IL-4 receptor complex in the anti-TCR-activated naive T cells and established cloned Th2 cells. The IL-4-induced activation of STAT5 appears to play an important role in the expansion process of the developing Th2 cells. Thus, the recruitment of Jak3 and STAT5 molecules to functional IL-4R complex in developing Th2 cells appears to be crucial for Th2 cell development.We demonstrated that the splenomegaly associated with Salmonella-infection, a host-defensive response, was caused by the migration of Mac-1^+ cells into the infected spleen. We tried to generate murine bone marrow-derived DC lines by using a helper-free and replication-defective recombinant retrovirus encoding the SV40 early antigens, and obtained several DC lines that can cytokine-independently grow.We established the mutant Listeria monocytogenes which expressed ply118 gene product when virulence genes are activated. We tried to establish the gene transduction system using this mutant Listeria.