脂多糖对抗原提呈细胞作用的影响

脂多糖的免疫调节效应能辅助机体的细胞免疫和体液免疫，促进机体的抗感染能力，但是大多数细菌脂多糖同时还有强的毒性作用，引起机体病理损伤。因此，了解脂多糖在免疫应答的重要环节——抗原提呈中的作用及其机制，对开发LPS的临床应用是非常重要的。     

抗原提呈细胞与天然免疫应答

抗原提呈细胞(APC)和自然杀伤细胞(NK)被激活后产生多种致炎细胞因子，如IL-12、IFN-γ和NO，它们在抗胞内病原体感染的天然免疫应答中起着极其重要的作用。本文阐述APC产生的细胞因子在天然免疫应答中的作用和天然免疫细胞因子对APC功能的调节作用。     

肠道粘膜免疫系统抗原提呈细胞研究进展

肠道粘膜免疫系统持续暴露于大量种类繁多的抗原,是病原体入侵的最大门户,因此抗原识别以及产生迅速有效的免疫反应对机体来说至关重要.免疫反应产生的一个限制性步骤是抗原识别、处理与呈递.参与肠道粘膜抗原提呈的细胞及分子数量多、种类多,相互作用复杂,并且有其特有的性质.     

脂多糖对抗原提呈细胞作用的影响

脂多糖的免疫调节效应能辅助机体的细胞免疫和体液免疫,促进机体的抗感染能力,但是大多数细菌脂多糖同时还有强的毒性作用,引起机体病理损伤。因此,了解脂多糖在免疫应答的重要环节——抗原提呈中的作用及其机制,对开发LPS的临床应用是非常重要的。     

胸腺基质细胞的抗原提呈作用

目的 研究胸腺基质细胞的抗原提呈能力。方法 应用ＯＶＡ－特异的、受Ｉ－Ａ＾ｄ分子识别限制的辅助Ｔ细胞杂交瘤（３ＤＯ．１８．３）识别提呈的ＯＶＡ的ＣＮＢｒ水解片段而被活化后产生ＩＬ－２,测定ＩＬ－２活性来分析胸腺基质细胞的抗原提呈作用。结果ＩＦＮ－γ能促进ＭＴＥＣＩ和ＭＴＳＣ４表达Ｉ－Ａ＾ｄ分子,并促进ＭＴＳＣ４表达Ｂ７－１分子。经ＩＦＮ－γ作用后,ＭＴＥＣ１和ＭＴＳＣ４均有抗原提呈能力,ＭＴＳＣ     

抗原提呈细胞与天然免疫应答

抗原提呈细胞(APC)和自然杀伤细胞(NK)被激活后产生多种致炎细胞因子,如IL12、IFNγ和NO,它们在抗胞内病原体感染的天然免疫应答中起着极其重要的作用。本文阐述APC产生的细胞因子在天然免疫应答中的作用和天然免疫细胞因子对APC功能的调节作用。     

086 抗原提呈的研究进展

抗原提呈过程涉及从抗原被提呈细胞摄取并消化成免疫原性肽,以ＭＨＣ肽复合物的形式呈现于细胞表面,通过ＴＣＲ激活Ｔ细胞,直至触发免疫应答反应的复杂过程。本文综述了抗原提呈的总过程,ＭＨＣ、肽、ＴＣＲ三者组装及其结构,免疫原性肽的胞内运输以及抗原交叉提呈等同最新进展。     

抗原提呈的研究进展

抗原提呈过程涉及从抗原被提呈细胞摄取并消化成免疫原性肽 ,以MHC 肽复合物的形式呈现于细胞表面 ,通过TCR激活T细胞 ,直至触发免疫应答反应的复杂过程。本文综述了抗原提呈的总过程 ,MHC、肽、TCR三者组装及其结构 ,免疫原性肽的胞内运输以及抗原交叉提呈等方面的最新进展。     

粘膜抗原提呈的研究进展

粘膜持续地暴露于大量种类繁多的抗原环境中 ,许多感染性病原体通过粘膜表面进入宿主 ,因此产生迅速有效的免疫反应对机体来说至关重要。大多数免疫反应产生的一个限制性步骤是抗原需通过辅佐细胞被提呈给T淋巴细胞 ,抗原的加工与提呈是免疫反应的一个中心事件。粘膜抗原可通过专职抗原提呈细胞和非专职抗原提呈细胞提呈。     

树突状细胞与其它APC抗原提呈功能及其作用机制比较

本文对ＤＣ与其它ＡＰＣ（Ｍψ，Ｂ细胞，在纤维细胞等）在抗原提呈功能及其作用机制，影响因素等方面进行了比较，以进一步明确ＤＣ的独特免疫功能。     

Natural killer cell cytotoxicity and its regulation by inhibitory receptors

Natural killer (NK) cells express an array of germ‐line encoded receptors that are capable of triggering cytotoxicity. NK cells tend to express many members of a given family of signalling molecules. The presence of many activating receptors and many members of a given family of signalling molecules can enable NK cells to detect different kinds of target cells, and to mount different kinds of responses. This contributes also to the robustness of NK cells responses; cytotoxic functions of NK cells often remain unaffected in the absence of selected signalling molecules. NK cells express many MHC‐I‐specific inhibitory receptors. Signals from MHC‐I‐specific inhibitory receptors tightly control NK cell cytotoxicity and, paradoxically, maintain NK cells in a state of proper responsiveness. This review provides a brief overview of the events that underlie NK cell activation, and how signals from inhibitory receptors intercept NK cell activation to prevent inappropriate triggering of cytotoxicity.     

青藤碱促进树突状细胞分化抑制其成熟

目的 探讨青藤碱对树突状细胞(Dendritic cell,DC)体外分化发育、成熟、抗原递呈及刺激T细胞活化能力的影响.方法 DC体外培养时,青藤碱处理,观察细胞生长情况,流式检测细胞表型及抗原内吞能力,混合淋巴细胞反应检测DC刺激T细胞活化的能力,E(I)ISA检测细胞因子分泌.结果 与对照组相比,青藤碱处理DCCD1a表达上调而CD14下调,IL-12分泌减少,共刺激分子表达减少,同种T细胞刺激活性降低.结论 合适剂量的青藤碱能刺激单核细胞分化为不成熟DC但能抑制其进一步成熟.     

Antibody-mediated delivery of antigen to chemokine receptors on antigen-presenting cells results in enhanced CD4+ T cell responses

Here, we have investigated if targeting of T cell epitopes to chemokine receptors results in improved CD4+ T cell responses. Mouse monoclonal antibodies (mAb) with kappaL chains were targeted to various chemokine receptors expressed on human monocytes or immature dendritic cells (DC), and proliferation of cloned human, DR4-restricted CD4+ T cells specific for mouse Ckappa(40-48) was measured. When using monocytes as antigen-presenting cells, mAb specific for CCR1, CCR2, CCR5, and CXCR4 were 100-10,000-fold more efficient at inducing T cell proliferation when compared to isotype-matched control mAb on a per molecule basis. Targeting of immature DC was less effective and was only seen with anti-CCR1 and anti-CXCR4 mAb. Anti-chemokine receptors mAb required to be processed by the conventional endosomal MHC class II presentation pathway. The mAb did not induce signaling through the chemokine receptors as they failed to induce mobilization of cytosolic Ca2+ and actin polymerization. They also failed to induce APC maturation. The results strongly suggest that chemokine receptors channel antigen into the endocytic pathway for presentation on MHC class II molecules. Targeting T cell epitopes to chemokine receptors by recombinant antibody should be a useful vaccine strategy for the induction of strong CD4+ T cell responses.     

On the mechanisms by which transforming growth factor-β2 alters antigen-presenting abilities of macrophages on T cell activation

Peritoneal exudate cells (PEC) incubated with antigen in the presence of transforming growth factor-(TGF)-β2 selectively suppress delayed hypersensitivity and IgG2a antibody production when injected intravenously into naive syngeneic recipients. In this study, we have examined in vitro the effects of TGF-β2 on the antigen presenting abilities of PEC to activate DO11.10 T cells that express a transgenic T cell receptor that recognizes ovalbumin peptide fragment 323–339 in the context of I-A^d. PEC were pretreated overnight with TGF-β2, washed extensively, then co-cultured with DO11.10 T cells in the presence of native OVA or P323–339. We found that TGF-β2-treated PEC induced the production of the T helper type 2 (Th2) cytokine, interleukin-4 (IL-4), but unlike untreated PEC, were unable to stimulate the Th1 cytokines, IL-2 and interferon-γ (IFN-γ). Furthermore, TGF-β2 was produced in an autocrine fashion by TGF-β2-treated PEC and was responsible for this shift to a Th2 response. This conclusion was supported by the following results. First, TGF-β2-treated PEC were found to express much more TGF-β1 and TGF-β2 mRNA than untreated PEC. Second, TGF-β2-treated PEC secreted large amounts of TGF-β including its mature form. Third, addition of neutralizing anti-TGF-β2 antibodies, but not neutralizing anti-TGF-β1 antibodies, restored the ability of antigen-pulsed, TGF-β2-pretreated PEC to stimulate DO11.10 T cells to secrete IL-2 and IFN-γ. These results indicate that antigen-presenting cells that encounter antigen in a TGF-β-enriched environment (e.g., in the eye) shift responding naive T cells toward Th2 responses by producing TGF-β during antigen presentation.     

Inhibition of T-cell responses by CD4 on an antigen-presenting cell

In addition to T-helper cells, CD4 is expressed on monocytes, macrophages and dendritic cells. To see whether CD4 molecules on antigen-presenting cells affect T-cell responses, we expressed CD4 on Raji cells, and compared positive and negative cells as stimulator cells for peripheral blood mononuclear cells in mixed lymphocyte reactions. We found that expression of CD4 on Raji had an inhibitory effect on production of IFN-gamma and other cytokines.     

Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells

The liver is known to induce tolerance rather than immunity through tolerogenic antigen presentation or elimination of effector T cells. In particular, hepatic dendritic cells (DC) are known to be little immunogenic for CD8 T cells. Here, we investigated whether this peculiar phenotype resulted from interaction with resident hepatic cell populations. Contact of DC with liver sinusoidal endothelial cells (LSEC) but not hepatocytes or B cells vetoed antigen-presenting DC to fully activate naive CD8 T cells. This MHC-independent regulatory effect of LSEC on DC function was not connected to soluble mediators but required physical contact. Because interaction with third-party LSEC still allowed antigen-presenting DC to stimulate expression of initial activation markers on naive CD8 T cells and to stimulate activated CD8 T cells, we hypothesize that LSEC controlled the DC costimulatory function. Indeed, contact with LSEC led to reduced DC expression levels of CD80/86 or IL-12, but supplementation of these signals failed to rescue the ability to prime naive CD8 T cells, indicating involvement of further molecules. Taken together, our results reveal a novel principle operative in hepatic tolerance induction, in which LSEC not only tolerize T cells themselves but also suppress neighboring APC normally capable of inducing T cell immunity.     

Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes

IL-10 is a potent anti-inflammatory cytokine interfering with antigen presentation by inducing the intracellular sequestration of MHC class II (MHC-II) molecules. Here we studied the contribution of membrane-associated RING-CH (MARCH) ubiquitin ligase family members to the IL-10-induced down-regulation of MHC-II molecules. We found that MARCH1 and MARCH8 proteins are the most potent family members for the down-regulation of MHC-II surface expression in transfected cells, but only MARCH1 mRNA expression is strongly induced by IL-10 in human primary monocytes. We detected mono- and poly-ubiquitinated forms of MHC-II molecules both in IL-10-treated monocytes and in cells transfected with MARCH1. We also show direct interaction between MHC-II and MARCH1 molecules in co-immunoprecipitation assays. Finally, we found that siRNA-mediated knockdown of MARCH1 reverses IL-10-induced MHC-II down-regulation in primary monocytes. Thus, the immunosuppressive effect of IL-10 on antigen presentation is mediated through induced expression of MARCH1.     

Immunosuppressive components of Ascaris suum down-regulate expression of costimulatory molecules and function of antigen-presenting cells via an IL-10-mediated mechanism

High-molecular-weight components (PI) of Ascaris suum suppress both cell-mediated and humoral responses against ovalbumin (OVA) via an IL-4/IL-10-dependent mechanism. The aim of this work was to investigate the effect of PI on the ability of APC to activate T cells and the role of IL-10 in this process. Flow cytometry analyses of MHC class II, CD80, CD86 and CD40 molecules on LN cells from mice immunized with OVA or OVA+PI showed that PI inhibits expression of these molecules on unfractionated cells and on purified CD11c(+) cells. A low proliferative response was obtained when OVA-specific TCR-Tg T cells were incubated with CD11c(+) cells from OVA+PI-immunized mice pulsed with OVA, when compared to those incubated with cells from OVA-immunized mice. Similar results were obtained using as APC CD11c(+) cells from OVA-immunized mice pulsed with OVA+PI, which also expressed less of the four markers. The inhibitory effect of PI on both the expression of costimulatory molecules and the induction of T cell proliferation was abolished in IL-10-deficient mice. Our data indicate that the potent immunosuppressive effect of A. suum extract components on the host immune system is primarily related to their property of down-regulating the Ag-presenting ability of DC via an IL-10-mediated mechanism.     

GITR/GITRL: more than an effector T cell co-stimulatory system

Glucocorticoid-induced TNFR-related protein (GITR) is a member of the TNFR superfamily, expressed in several cells and tissues including T lymphocytes, NK cells and antigen-presenting cells (APC). GITR activation, upon interaction with its ligand (GITRL), functions as a co-activating signal. GITRL is mainly expressed on APC and GITR/GITRL interaction is important for the development of immune response. This review summarizes recent results about the GITR/GITRL system, focusing on the interplay between APC, effector and regulatory T cells.