共查询到20条相似文献，搜索用时 31 毫秒
1.
Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles 总被引：1，自引：0，他引：1
Kiss EA Vonarbourg C Kopfmann S Hobeika E Finke D Esser C Diefenbach A 《Science (New York, N.Y.)》2011,334(6062):1561-1565
2.
Dudakov JA Hanash AM Jenq RR Young LF Ghosh A Singer NV West ML Smith OM Holland AM Tsai JJ Boyd RL van den Brink MR 《Science (New York, N.Y.)》2012,336(6077):91-95
Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant RORγ(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence. 相似文献
3.
Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells 总被引：1，自引：0，他引：1
Intestinal intraepithelial T lymphocytes (IELs) are likely to play a key role in host mucosal immunity and, unlike other T cells, have been proposed to differentiate from local precursors rather than from thymocytes. We show here that IELs expressing the alphabeta T cell receptor are derived from precursors that express RORgammat, an orphan nuclear hormone receptor detected only in immature CD4+CD8+ thymocytes, fetal lymphoid tissue-inducer (LTi) cells, and LTi-like cells in cryptopatches within the adult intestinal lamina propria. Using cell fate mapping, we found that all intestinal alphabeta T cells are progeny of CD4+CD8+ thymocytes, indicating that the adult intestine is not a significant site for alphabeta T cell development. Our results suggest that intestinal RORgammat+ cells are local organizers of mucosal lymphoid tissue. 相似文献
4.
Sonnenberg GF Monticelli LA Alenghat T Fung TC Hutnick NA Kunisawa J Shibata N Grunberg S Sinha R Zahm AM Tardif MR Sathaliyawala T Kubota M Farber DL Collman RG Shaked A Fouser LA Weiner DB Tessier PA Friedman JR Kiyono H Bushman FD Chang KM Artis D 《Science (New York, N.Y.)》2012,336(6086):1321-1325
The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. 相似文献
5.
Epstein JE Tewari K Lyke KE Sim BK Billingsley PF Laurens MB Gunasekera A Chakravarty S James ER Sedegah M Richman A Velmurugan S Reyes S Li M Tucker K Ahumada A Ruben AJ Li T Stafford R Eappen AG Tamminga C Bennett JW Ockenhouse CF Murphy JR Komisar J Thomas N Loyevsky M Birkett A Plowe CV Loucq C Edelman R Richie TL Seder RA Hoffman SL 《Science (New York, N.Y.)》2011,334(6055):475-480
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria. 相似文献
6.
目的研究小鼠脾Th17细胞分化模型中IL-17F、RORα、Stat3表达。方法提取C57/BL6J小鼠脾淋巴细胞,采用免疫磁珠纯化CD4-＋CD62L-＋T细胞,分为对照组及Th17分化组。对照组用RPMI1640培养;Th17分化组加抗小鼠CD3ε、CD28、IFN-γ、IL-4单抗及IL-6、TGF-β1、IL-23孵育。培养48 h后,采用Real-time PCR检测两组细胞IL-17F、RORα、Stat3 mRNA表达。结果 Th17分化组IL-17F、RORα、Stat3 mRNA表达明显高于对照组（P〈0.01）。结论小鼠脾Th17细胞分化过程中伴有RORα、Stat3 mRNA表达上调。 相似文献
7.
Zhang Z Schuler T Zupancic M Wietgrefe S Staskus KA Reimann KA Reinhart TA Rogan M Cavert W Miller CJ Veazey RS Notermans D Little S Danner SA Richman DD Havlir D Wong J Jordan HL Schacker TW Racz P Tenner-Racz K Letvin NL Wolinsky S Haase AT 《Science (New York, N.Y.)》1999,286(5443):1353-1357
In sexual transmission of simian immunodeficiency virus, and early and later stages of human immunodeficiency virus-type 1 (HIV-1) infection, both viruses were found to replicate predominantly in CD4(+) T cells at the portal of entry and in lymphoid tissues. Infection was propagated not only in activated and proliferating T cells but also, surprisingly, in resting T cells. The infected proliferating cells correspond to the short-lived population that produces the bulk of HIV-1. Most of the HIV-1-infected resting T cells persisted after antiretroviral therapy. Latently and chronically infected cells that may be derived from this population pose challenges to eradicating infection and developing an effective vaccine. 相似文献
8.
9.
Mora JR Iwata M Eksteen B Song SY Junt T Senman B Otipoby KL Yokota A Takeuchi H Ricciardi-Castagnoli P Rajewsky K Adams DH von Andrian UH 《Science (New York, N.Y.)》2006,314(5802):1157-1160
Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators. 相似文献
10.
AG Schepers HJ Snippert DE Stange M van den Born JH van Es M van de Wetering H Clevers 《Science (New York, N.Y.)》2012,337(6095):730-735
The concept that tumors are maintained by dedicated stem cells, the so-called cancer stem cell hypothesis, has attracted great interest but remains controversial. Studying mouse models, we provide direct, functional evidence for the presence of stem cell activity within primary intestinal adenomas, a precursor to intestinal cancer. By "lineage retracing" using the multicolor Cre-reporter R26R-Confetti, we demonstrate that the crypt stem cell marker Lgr5 (leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5) also marks a subpopulation of adenoma cells that fuel the growth of established intestinal adenomas. These Lgr5(+) cells, which represent about 5 to 10% of the cells in the adenomas, generate additional Lgr5(+) cells as well as all other adenoma cell types. The Lgr5(+) cells are intermingled with Paneth cells near the adenoma base, a pattern reminiscent of the architecture of the normal crypt niche. 相似文献
11.
Murata S Sasaki K Kishimoto T Niwa S Hayashi H Takahama Y Tanaka K 《Science (New York, N.Y.)》2007,316(5829):1349-1353
Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i selectively reduces this activity. We also found that beta5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection. 相似文献
12.
鸡马立克氏病疫苗免疫后的免疫学变化 总被引：1，自引：0，他引：1
实验对１日龄雏鸡接种ＭＤ三价疫苗或ＨＶＴ疫苗后的免疫应答变化进行了检测．发现ＭＤ疫苗免疫后：（１）脾脏、胸腺Ｔ细胞ＩＬ—２诱生活性和ＩＬ—２Ｒ表达明显增强或增多，表明ＩＬ—２的免疫调节作用增强；（２）胸腺、法氏囊和脾脏中Ｔ细胞和抗体生成细胞数量及Ｔ细胞增殖功能明显增高，表明中枢与外周免疫器官的细胞免疫和体液免疫应答显著增强；（３）盲肠扁桃体、哈德尔腺、支气管粘膜淋巴组织中Ｔ细胞和抗体生成细胞数量以及泪液、气管液、肠液、胆汁中ＩｇＡ，ＩｇＧ，ＩｇＭ含量明显增多，表明呼吸道与消化道的局部免疫应答也显著增强；（４）ＭＤ三价疫苗免疫鸡的上述免疫应答变化比ＨＶＴ疫苗免疫鸡明显． 相似文献
13.
Maeda T Merghoub T Hobbs RM Dong L Maeda M Zakrzewski J van den Brink MR Zelent A Shigematsu H Akashi K Teruya-Feldstein J Cattoretti G Pandolfi PP 《Science (New York, N.Y.)》2007,316(5826):860-866
Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell-instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage. 相似文献
14.
Mucida D Park Y Kim G Turovskaya O Scott I Kronenberg M Cheroutre H 《Science (New York, N.Y.)》2007,317(5835):256-260
The cytokine transforming growth factor-beta (TGF-beta) converts na?ve T cells into regulatory T (Treg) cells that prevent autoimmunity. However, in the presence of interleukin-6 (IL-6), TGF-beta has also been found to promote the differentiation of na?ve T lymphocytes into proinflammatory IL-17 cytokine-producing T helper 17 (T(H)17) cells, which promote autoimmunity and inflammation. This raises the question of how TGF-beta can generate such distinct outcomes. We identified the vitamin A metabolite retinoic acid as a key regulator of TGF-beta-dependent immune responses, capable of inhibiting the IL-6-driven induction of proinflammatory T(H)17 cells and promoting anti-inflammatory Treg cell differentiation. These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity. 相似文献
15.
Epithelial cells respond to physicochemical damage with up-regulation of major histocompatibility complex-like ligands that can activate the cytolytic potential of neighboring intraepithelial T cells by binding the activating receptor, NKG2D. The systemic implications of this lymphoid stress-surveillance response, however, are unknown. We found that antigens encountered at the same time as cutaneous epithelial stress induced strong primary and secondary systemic, T helper 2 (T(H)2)-associated atopic responses in mice. These responses required NKG2D-dependent communication between dysregulated epithelial cells and tissue-associated lymphoid cells. These data are germane to uncertainty over the afferent induction of T(H)2 responses and provide a molecular framework for considering atopy as an important component of the response to tissue damage and carcinogenesis. 相似文献
16.
以仔猪小肠上皮细胞为模型,应用实时荧光定量PCR方法测定相关基因指标,研究刺五加苷B(EB)对仔猪小肠上皮(IPEC-J2)细胞紧密连接蛋白及炎性细胞因子mRNA表达量的影响。结果表明:0.1 mg/m L刺五加苷B显著增强肠道细胞紧密连接蛋白Occludin、Claudin-3、ZO-1和抗炎性细胞因子IL-10和TGF-β的mRNA表达量,且减弱促炎性细胞因子IL-6、TNF-α、INF-γ的mRNA表达量。说明刺五加苷B可通过改变细胞间紧密连接蛋白和细胞因子的表达从而对维持肠道屏障功能的完整性起到促进作用,有益于仔猪肠道的健康发育。 相似文献
17.
The experiment was conducted to study the dynamic changes of immune responses of chicks immunized with Marck‘s disease(MD) trivalent vaccine and turkey herpesvirus (HVT)at one day age.Results were found that after immunization of chicks with MD vaccines,the interlcukine-2 (IL-2) inductive activity and IL-2 receptor expression of T cells from thymus and spleen significantly increased.suggesting that the immunoregulative function was markedly enhanced in the immune organs;the number of antibody-producing cells,the number and proliferative function of T cells rose markedly in Bursa Fabricius,Splcen and thymus,indicating that the ccllular and humoral immune responses were elevated remarkablly in the central and peripheral immune organs; the number of T and antibody-producing cells as well as the content of IgG,IgA and IgM obviously mounted in cecal tonsil,Harder ian gland mucosal lymphoid tissucs of bronchus along with tears,trachea washings,bilc and intestinal fluids,demonstrating that the local and mucosal immunity was raised in the respiratory and digestive tract;the levels of immune responses mentioned above in the trivalent vaccine-immuniacd chicks were apparently higher than those of HVT-immunized birds. 相似文献
18.
为了建立一套犬IFN-γ(cIFN-γ)在HEK293T细胞中表达的方法,用伴刀豆球蛋白A(ConA)刺激犬脾细胞,通过RT-PCR方法从脾细胞中扩增犬IFN-γ基因,并将其克隆到pcDNA3.1A载体中,构建的真核表达载体pcDNA3.1A-cIFN-γ经磷酸钙介导转染HEK293T细胞进行表达。结果表明:克隆的犬IFN-γcDNA基因与GenBank上发表的序列一致,同源性100%。表达产物经Western-blot方法检测,证明克隆的犬IFN-γ基因能够在HEK293T细胞中进行表达,并且表达产物能够分泌到细胞外。 相似文献
19.
Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora 总被引：1，自引：0，他引：1
Fagarasan S Muramatsu M Suzuki K Nagaoka H Hiai H Honjo T 《Science (New York, N.Y.)》2002,298(5597):1424-1427
Activation-induced cytidine deaminase (AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid follicles (ILFs) associated with a 100-fold expansion of anaerobic flora in the small intestine. Reduction of bacterial flora by antibiotic treatment of AID-/- mice abolished ILF hyperplasia as well as the germinal center enlargement seen in secondary lymphoid tissues. Because an inability to switch to immunoglobulin A on its own does not lead to a similar phenotype, these results suggest that SHM of ILF B cells plays a critical role in regulating intestinal microflora. 相似文献
20.
Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells 总被引：36，自引：0，他引：36
Several pathways of transmembrane signaling in lymphocytes involve protein-tyrosine phosphorylation. With the exception of p56lck, a tyrosine kinase specific to T lymphoid cells that associates with the T cell transmembrane proteins CD4 and CD8, the kinases that function in these pathways are unknown. A murine lymphocyte complementary DNA that represents a new member of the src family has now been isolated and characterized. This complementary DNA, termed blk (for B lymphoid kinase), specifies a polypeptide of 55 kilodaltons that is related to, but distinct from, previously identified retroviral or cellular tyrosine kinases. The protein encoded by blk exhibits tyrosine kinase activity when expressed in bacterial cells. In the mouse and among cell lines, blk is specifically expressed in the B cell lineage. The tyrosine kinase encoded by blk may function in a signal transduction pathway that is restricted to B lymphoid cells. 相似文献