Pertussis toxin (PTX) has been widely used as an adjuvant to induce Th1-mediated organ-specific autoimmune diseases in animal models. However, the cellular and molecular mechanisms remain to be defined. In this study, we showed that dendritic cells (DC) stimulated with PTX (PTX-DC) were able to substitute for PTX to promote experimental autoimmune uveitis (EAU). EAU induced by PTX-DC revealed a typical Th1 response, characterized by high uveitogenic retinal Ag interphotoreceptor retinoidbinding protein (IRBP)-specific IFN-and IL-12 production in the draining lymph nodes, as well as increased levels of anti-IRBP IgG2a and decreased levels of anti-IRBP IgG1 in the serum of IRBP-immunized mice. Furthermore, PTX-DC preferentially induced T cells to produce the Th1 cytokine, IFN-. After being stimulated with PTX, DC exhibited up-regulation of MHC class II, CD80, CD86, CD40, and DEC205. PTX-DC had also increased allostimulatory capacity and IL-12 and TNF-production. Serum IL-12 was increased in naive mice that received PTX-DC i.p. In addition, PTX activated extracellular signal-regulated kinase in DC. Following the inhibition of extracellular signal-regulated kinase signaling, the maturation of PTX-DC was reduced. Subsequently, the ability of PTX-DC to promote IFN-production by T cells in vitro and to induce EAU in vivo was blocked. The results suggest that PTX might exert an adjuvant effect on DC to promote their maturation and the production of proinflammatory cytokines, thereby eliciting a Th1 response.

目的 研究人转化生长因子βl（TGFβ1）基因修饰对大鼠骨髓树突状细胞（DC）免疫功能的影响。方法 构建TCFβ1-pcDNA3质粒并转染未成熟DC。检测转染后DC的TGFβ1表达及其功能变化，输注l周后检测TGFβ1-DC在受者睥和淋巴结的分布、T细胞捅亡水平及T绳胞端粒酶表达。结果 TGFβ1-pcDNA3船最粒转染Dc能有效抑制DC的成熟和分化，并下调DC的多种功能。TG即1基因转染不仅能降低DC对LPS的反应，同时抑制DC在MLR中刺激T细胞增殖的能力。TGFβ1-DC输注受者后，l周内可在脾和淋巴结内形成微嵌合，并有效诱导T细胞的凋亡，抑制T细胞端粒酶的活性和表达。结论 TGFβl基因能有效抑制DC的多种功能，可用于诱导机体免疫耐受。

目的 探讨在小鼠树突状细胞（DC）成熟过程中核因子-kB（NF-kB）基因的作用。方法 应用特异性NF-kB寡聚脱氧核甘酸诱骗剂（NF-kBODNDecoys）阻断NF-kB活性，观察DC形态、细胞表面分子表达以及同种T淋巴细胞增殖反应的变化，了解NF-kB其因对DC成熟及免疫生物活性的影响。结果 NF-kBODNDecoys的有效摄取，抑制了DC表面共刺激分子CD80、CD86、CD40的表达和白细胞介素12（IL-12）的分泌，阻碍了DC的发育成熟，这种阻碍作用不可被脂多糖（LPS）所逆转。混合淋巴细胞反应显示，NF-kBODNDecoys的应用可诱导DC刺激同种T淋巴细胞低反应活性，抑制了T细胞IL-2和y-十扰素（IFN-y）的分泌。结论 NF-kB是DC发育成熟过程中关键性调控基因。应用NF-KbODNDecoys可抑制DC的成熟，从而为生成耐受原性未成熟DC、诱导移植免疫耐受提供了一种新的途径。

Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein expressed predominantly in prostate secretory acinar epithelium and prostate cancer cells as well as in several extraprostatic tissues. Mouse monoclonal antibody 4G5 specific to the extracellular domain of PSMA was used to screen two phage displayed peptide libraries (9aa linear and 9aa cys library). Three 4G5-reactive phagotopes were identified. Sequence analysis of isolated clones demonstrated that the interaction motif VDPA/SK has high homology to 719-725aa on PSMA. Immunohistochemical staining of the prostate cancer sample with the PSMA-mimic phagotope (mimotope) immunized serum antibodies demonstrate that the mimotope isolated from the phage displayed peptide libraries can induce PSMA specific immune response in vivo.

We investigated whether recipient dendritic cells (DCs), pretreated with nuclear factor-kB oligodeoxyribonucleotide decoy (NF-kB ODN decoy) and loaded with ultraviolet B-irradiated donor apoptotic splenocytes (Apo-SCs), were able to induce murine cardiac allograft tolerance. Heterotopic vascularized heart transplantation was performed from BALB/c to C57BL/6 mice, and recipients (C57BL/6) were given one injection of recipient DCs pretreated with NF-kB ODN decoy and loaded with donor (BALB/c) apoptotic SCs (decoy Apo-SCs DCs) through the portal vein at 7 days, before heart transplantation in the absence of immunosuppression. The cardiac allograft survival time and the expressive levels of intragraft cytokine genes [interleukin (IL)-2, IL-10, and interferon-γ] were evaluated. Our results indicated that injection of decoy Apo-SCs DCs significantly prolonged vascularized heart allograft survival and led to skewing of intragraft cytokine expression towards T helper 2 (IL-10). The mechanisms can be useful for therapy of allograft rejection with minimization of systemic immunosuppression.