共查询到20条相似文献，搜索用时 15 毫秒
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Rissoan MC Soumelis V Kadowaki N Grouard G Briere F de Waal Malefyt R Liu YJ 《Science (New York, N.Y.)》1999,283(5405):1183-1186
It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-gamma. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset. 相似文献
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Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production 总被引：13，自引：0，他引：13
Engagement of the antigen-specific receptor (TCR) of CD4+ T lymphocytes without a second (costimulatory) signal prevents the subsequent production of interleukin-2 (IL-2) by these cells. Because IL-2 is a key immunoregulatory lymphokine and is also produced by a subset of CD8+ T cells that are able to kill target cells, the effect of engaging the TCR of one such clone in the absence of costimulatory signals was examined. The capacity for TCR-dependent IL-2 production was lost, indicating comparable costimulator-dependent signaling requirements for IL-2 production in CD4+ and CD8+ T cells. However, TCR-mediated cytotoxicity was not impaired, implying that costimulation is required for only certain TCR-dependent effector functions. 相似文献
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CTLA-4 control over Foxp3+ regulatory T cell function 总被引：1，自引：0，他引：1
Wing K Onishi Y Prieto-Martin P Yamaguchi T Miyara M Fehervari Z Nomura T Sakaguchi S 《Science (New York, N.Y.)》2008,322(5899):271-275
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells. 相似文献
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Jenkins SJ Ruckerl D Cook PC Jones LH Finkelman FD van Rooijen N MacDonald AS Allen JE 《Science (New York, N.Y.)》2011,332(6035):1284-1288
A defining feature of inflammation is the accumulation of innate immune cells in the tissue that are thought to be recruited from the blood. We reveal that a distinct process exists in which tissue macrophages undergo rapid in situ proliferation in order to increase population density. This inflammatory mechanism occurred during T helper 2 (T(H)2)-related pathologies under the control of the archetypal T(H)2 cytokine interleukin-4 (IL-4) and was a fundamental component of T(H)2 inflammation because exogenous IL-4 was sufficient to drive accumulation of tissue macrophages through self-renewal. Thus, expansion of innate cells necessary for pathogen control or wound repair can occur without recruitment of potentially tissue-destructive inflammatory cells. 相似文献
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Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation 总被引：2，自引：0，他引：2
The mechanisms that allow antigen-presenting cells (APCs) to selectively present extracellular antigen to CD8+ effector T cells (cross-presentation) or to CD4+ T helper cells are not fully resolved. We demonstrated that APCs use distinct endocytosis mechanisms to simultaneously introduce soluble antigen into separate intracellular compartments, which were dedicated to presentation to CD8+ or CD4+ T cells. Specifically, the mannose receptor supplied an early endosomal compartment distinct from lysosomes, which was committed to cross-presentation. These findings imply that antigen does not require intracellular diversion to access the cross-presentation pathway, because it can enter the pathway already during endocytosis. 相似文献
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Barouch DH Santra S Schmitz JE Kuroda MJ Fu TM Wagner W Bilska M Craiu A Zheng XX Krivulka GR Beaudry K Lifton MA Nickerson CE Trigona WL Punt K Freed DC Guan L Dubey S Casimiro D Simon A Davies ME Chastain M Strom TB Gelman RS Montefiori DC Lewis MG Emini EA Shiver JW Letvin NL 《Science (New York, N.Y.)》2000,290(5491):486-492
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+ T cells, no virus-specific CD4+ T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+ T cell counts, preserved virus-specific CD4+ T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge. 相似文献
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Memory T cells maintain their numbers for long periods after antigen exposure. Here we show that CD8+ T cells of memory phenotype divide slowly in animals. This division requires interleukin-15 and is markedly increased by inhibition of interleukin-2 (IL-2). Therefore, the numbers of CD8+ memory T cells in animals are controlled by a balance between IL-15 and IL-2. 相似文献
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为了观察马齿苋多糖(Portulace oleracea polysaccharide,POP)对雏鸡胸腺免疫功能的影响,并探讨其可能的作用机制,试验通过对雏鸡灌注不同剂量的POP,测定雏鸡胸腺指数,应用MMT(四甲基偶氮唑盐比色法)方法测定雏鸡胸腺淋巴细胞转化率,利用流式细胞器测定雏鸡胸腺淋巴细胞周期与胸腺T淋巴细胞亚群的变化.结果表明,POP能显著增加雏鸡胸腺淋巴细胞转化率和胸腺指数(P＜0.05),淋巴细胞增殖指数显著提高(P＜0.05),CD4+T淋巴细胞含量显著增加(P＜0.05),CD8+T淋巴细胞数量变化不明显,CD4+/CD8+T淋巴细胞比值显著升高(P＜0.05).POP可通过调节雏鸡胸腺内细胞水平的变化,增强雏鸡细胞免疫功能,促进免疫系统发育. 相似文献
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Savage PA Vosseller K Kang C Larimore K Riedel E Wojnoonski K Jungbluth AA Allison JP 《Science (New York, N.Y.)》2008,319(5860):215-220
Substantial evidence exists that many tumors can be specifically recognized by CD8+ T lymphocytes. The definition of antigens targeted by these cells is paramount for the development of effective immunotherapeutic strategies for treating human cancers. In a screen for endogenous tumor-associated T cell responses in a primary mouse model of prostatic adenocarcinoma, we identified a naturally arising CD8+ T cell response that is reactive to a peptide derived from histone H4. Despite the ubiquitous nature of histones, T cell recognition of histone H4 peptide was specifically associated with the presence of prostate cancer in these mice. Thus, the repertoire of antigens recognized by tumor-infiltrating T cells is broader than previously thought and includes peptides derived from ubiquitous self antigens that are normally sequestered from immune detection. 相似文献
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【目的】提高猪繁殖与呼吸综合征病毒（PRRSV）基因免疫的效果,构建含CpG基序和PRRSV ORF5的真核重组表达质粒CpG-pVAX1-ORF5。【方法】经酶切鉴定和序列测定,将重组质粒转染COS-7细胞,经间接免疫荧光试验证实CpG-pVAX1-ORF5可表达PRRSV GP5蛋白。免疫SPF小鼠,检测鼠的特异性抗体滴度、脾T淋巴细胞亚群数量（CD4+和CD8+）以及淋巴细胞增殖反应（MTT法）水平。【结果】本试验构建的含CpG基序真核重组表达质粒CpG-pVAX1-ORF5能诱导小鼠产生针对PRRSV的体液免疫与细胞免疫。【结论】CpG-ODN可提高PRRSV基因疫苗的免疫效果。 相似文献
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Mounting a protective immune response is critically dependent on the orchestrated movement of cells within lymphoid organs. We report here the visualization, using major histocompatability complex class I tetramers, of the CD8-positive (CD8) T cell response in the spleens of mice to Listeria monocytogenes infection. A multistage pathway was revealed that included initial activation at the borders of the B and T cell zones followed by cluster formation with antigenpresenting cells leading to CD8 T cell exit to the red pulp via bridging channels. Strikingly, many memory CD8 T cells localized to the B cell zones and, when challenged, underwent rapid migration to the T cell zones where proliferation occurred, followed by egress via bridging channels in parallel with the primary response. Thus, the ability to track endogenous immune responses has uncovered both distinct and overlapping mechanisms and anatomical locations driving primary and secondary immune responses. 相似文献
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Thymocyte expression of RAG-1 and RAG-2: termination by T cell receptor cross-linking. 总被引：30，自引：0，他引：30
L A Turka D G Schatz M A Oettinger J J Chun C Gorka K Lee W T McCormack C B Thompson 《Science (New York, N.Y.)》1991,253(5021):778-781
The expression of the V(D)J [variable (diversity) joining elements] recombination activating genes, RAG-1 and RAG-2, has been examined during T cell development in the thymus. In situ hybridization to intact thymus and RNA blot analysis of isolated thymic subpopulations separated on the basis of T cell receptor (TCR) expression demonstrated that both TCR- and TCR+ cortical thymocytes express RAG-1 and RAG-2 messenger RNA's. Within the TCR+ population, RAG expression was observed in immature CD4+CD8+ (double positive) cells, but not in the more mature CD4+CD8- or CD4-CD8+ (single positive) subpopulations. Thus, although cortical thymocytes that bear TCR on their surface continue to express RAG-1 and RAG-2, it appears that the expression of both genes is normally terminated during subsequent thymic maturation. Since thymocyte maturation in vivo is thought to be regulated through the interaction of the TCR complex with self major histocompatibility complex (MHC) antigens, these data suggest that signals transduced by the TCR complex might result in the termination of RAG expression. Consistent with this hypothesis, thymocyte TCR cross-linking in vitro led to rapid termination of RAG-1 and RAG-2 expression, whereas cross-linking of other T cell surface antigens such as CD4, CD8, or HLA class I had no effect. 相似文献
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Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4 总被引：31，自引：0，他引：31
P T Golumbek A J Lazenby H I Levitsky L M Jaffee H Karasuyama M Baker D M Pardoll 《Science (New York, N.Y.)》1991,254(5032):713-716
The generation of antigen-specific antitumor immunity is the ultimate goal in cancer immunotherapy. When cells from a spontaneously arising murine renal cell tumor were engineered to secrete large doses of interleukin-4 (IL-4) locally, they were rejected in a predominantly T cell-independent manner. However, animals that rejected the IL-4-transfected tumors developed T cell-dependent systemic immunity to the parental tumor. This systemic immunity was tumor-specific and primarily mediated by CD8+ T cells. Established parental tumors could be cured by the systemic immune response generated by injection of the genetically engineered tumors. These results provide a rationale for the use of lymphokine gene-transfected tumor cells as a modality for cancer therapy. 相似文献
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Pagès G Guérin S Grall D Bonino F Smith A Anjuere F Auberger P Pouysségur J 《Science (New York, N.Y.)》1999,286(5443):1374-1377
The p42 and p44 mitogen-activated protein kinases (MAPKs), also called Erk2 and Erk1, respectively, have been implicated in proliferation as well as in differentiation programs. The specific role of the p44 MAPK isoform in the whole animal was evaluated by generation of p44 MAPK-deficient mice by homologous recombination in embryonic stem cells. The p44 MAPK-/- mice were viable, fertile, and of normal size. Thus, p44 MAPK is apparently dispensable and p42 MAPK (Erk2) may compensate for its loss. However, in p44 MAPK-/- mice, thymocyte maturation beyond the CD4+CD8+ stage was reduced by half, with a similar diminution in the thymocyte subpopulation expressing high levels of T cell receptor (CD3high). In p44 MAPK-/- thymocytes, proliferation in response to activation with a monoclonal antibody to the T cell receptor in the presence of phorbol myristate acetate was severely reduced even though activation of p42 MAPK was more sustained in these cells. The p44 MAPK apparently has a specific role in thymocyte development. 相似文献
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雏鸡免疫柔嫩艾美耳球虫早熟株和毒株的细胞免疫反应 总被引：3，自引：0，他引：3
AA肉鸡雏鸡分别经口免疫柔嫩艾美耳球虫毒株早熟株，用免疫组化ABC法染色检测小肠、盲肠扁桃体、脾脏中CD4^ 、CD8^ T淋巴细胞动态变化；用淋巴细胞转化实验MTT法检测T淋巴细胞活性。结果表明：球虫免疫鸡后，CD4^ T淋巴细胞在一次免疫后迅速增殖，第6天达到第一峰，免疫柔嫩艾美耳球虫毒株的鸡盲肠与脾脏中CD4^ T淋巴细胞占所有淋巴细胞百分率分别达到38％和44％，免疫早熟株的鸡盲肠与脾脏中CD4^ T淋巴细胞占所有淋巴细胞百分率分别达到36％和43％，而二次免疫后和对照相比很少有显著差异。CD8^ T淋巴细胞在一次免疫后比CD4^ T增殖速度慢，第9天达到第一峰。免疫柔嫩艾美耳球虫毒株的鸡在此日盲肠与脾脏中CD8^ T淋巴细胞占所有淋巴细胞百分率分别达到37％和47％，免疫早熟株的鸡在此日盲肠与脾脏中CD8^ T淋巴细胞占所有淋巴细胞百分率分别达到36％和48％，二次免疫后迅速大量增殖，免疫柔嫩艾美耳球虫毒株的鸡在二免后第2天盲肠与脾脏中CD8^ T淋巴细胞占所有淋巴细胞百分率分别达到39％和50％．免疫柔嫩艾美耳球虫早熟株的鸡在二免后第2天盲肠与脾脏中CD8^ T淋巴细胞占所有淋巴细胞百分率分别达到37％和50％。且CD8^ T淋巴细胞总体水平比CD4^ T淋巴细胞多。盲肠扁桃体中T细胞的增殖速度比其他组织更快。免疫早熟株的鸡与免疫毒株的鸡肠道黏膜中的CD4^ 、CD8^ T淋巴细胞变化基本一致。一次免疫鸡比未免疫对照T淋巴细胞活性显著升高；进行二免的鸡免疫后第一、二、三周T淋巴细胞活性均比未进行二免的鸡显著升高；毒株免疫鸡T淋巴细胞活性大多与早熟株免疫鸡无8显著差异。 相似文献
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Randolph DA Huang G Carruthers CJ Bromley LE Chaplin DD 《Science (New York, N.Y.)》1999,286(5447):2159-2162
Subsets of murine CD4+ T cells localize to different areas of the spleen after adoptive transfer. Na?ve and T helper 1 (TH1) cells, which express the chemokine receptor CCR7, are home to the periarteriolar lymphoid sheath, whereas activated TH2 cells, which lack CCR7, form rings at the periphery of the T cell zones near B cell follicles. Retroviral transduction of TH2 cells with CCR7 forces them to localize in a TH1-like pattern and inhibits their participation in B cell help in vivo but not in vitro. Thus, differential expression of chemokine receptors results in unique cellular migration patterns that are important for effective immune responses. 相似文献