共查询到20条相似文献，搜索用时 31 毫秒
1.
Langerhans' cells migrating from contact-sensitized skin were found to up-regulate expression of macrophage-derived chemokine (MDC) during maturation into lymph node dendritic cells (DCs). Na?ve T cells did not migrate toward MDC, but antigen-specific T cells rapidly acquired MDC responsiveness in vivo after a subcutaneous injection of antigen. In chemotaxis assays, maturing DCs attracted activated T cells more strongly than na?ve T cells. These studies identified chemokine up-regulation as part of the Langerhans' cell maturation program to immunogenic T cell-zone DC. Preferential recruitment of activated T cells may be a mechanism used by maturing DCs to promote encounters with antigen-specific T cells. 相似文献
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Immunity to a plethora of microbes depends on a diverse repertoire of na?ve lymphocytes and the production of long-lived memory cells. We present evidence here that low clonal abundance in a polyclonal repertoire favors the survival and activation of na?ve CD4(+) T cells as well as the survival of their memory cell progeny. The inverse relation between clonal frequency and survival suggests that intraclonal competition could help maintain an optimally diverse repertoire of T cells and an optimal environment for the generation of long-lived memory cells. 相似文献
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Gu Y Filippi MD Cancelas JA Siefring JE Williams EP Jasti AC Harris CE Lee AW Prabhakar R Atkinson SJ Kwiatkowski DJ Williams DA 《Science (New York, N.Y.)》2003,302(5644):445-449
The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function. 相似文献
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A central question in immunology is the origin of long-lived T cell memory that confers protection against recurrent infection. The differentiation of na?ve T cell receptor transgenic CD8+ cells into effector cytotoxic T lymphocytes (CTLs) and memory CD8+ cells was studied. Memory CD8+ cells that were generated after strong antigenic stimulation were the progeny of cytotoxic effectors and retained antigen-specific cytolytic activity 10 weeks after adoptive transfer to antigen-free recipient mice. Thus, potential vaccines based on CTL memory will require the differentiation of na?ve cells into post-effector memory T cells. 相似文献
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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
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Interactions between the T cell receptor (TCR) and major histocompatibility complex antigens are essential for the survival and homeostasis of peripheral T lymphocytes. However, little is known about the TCR signaling events that result from these interactions. The peripheral T cell pool of p56lck (lck)-deficient mice was reconstituted by the expression of an inducible lck transgene. Continued survival of peripheral na?ve T cells was observed for long periods after switching off the transgene. Adoptive transfer of T cells from these mice into T lymphopoienic hosts confirmed that T cell survival was independent of lck but revealed its essential role in TCR-driven homeostatic proliferation of na?ve T cells in response to the T cell-deficient host environment. These data suggest that survival and homeostatic expansion depend on different signals. 相似文献
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In contrast to na?ve T cells that recognize short antigen-derived peptides displayed by specialized antigen-presenting cells, immunoglobulin receptors of B lymphocytes primarily recognize intact proteins. How and where within a lymph node such unprocessed antigens become available for na?ve B cell recognition is not clear. We used two-photon intravital imaging to show that, after exiting high-endothelial venules and before entry into lymph node follicles, B cells survey locally concentrated dendritic cells. Engagement of the B cell receptor by the dendritic cell (DC)-associated antigen leads to lymphocyte calcium signaling, migration arrest, antigen acquisition, and extrafollicular accumulation. These findings suggest a possible role for antigen-specific B-DC interactions in promoting T cell-dependent antibody responses in vivo. 相似文献
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Kraynov VS Chamberlain C Bokoch GM Schwartz MA Slabaugh S Hahn KM 《Science (New York, N.Y.)》2000,290(5490):333-337
Signaling proteins are thought to be tightly regulated spatially and temporally in order to generate specific and localized effects. For Rac and other small guanosine triphosphatases, binding to guanosine triphosphate leads to interaction with downstream targets and regulates subcellular localization. A method called FLAIR (fluorescence activation indicator for Rho proteins) was developed to quantify the spatio-temporal dynamics of the Rac1 nucleotide state in living cells. FLAIR revealed precise spatial control of growth factor-induced Rac activation, in membrane ruffles and in a gradient of activation at the leading edge of motile cells. FLAIR exemplifies a generally applicable approach for examining spatio-temporal control of protein activity. 相似文献
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Mammalian epidermis is maintained by self-renewal of stem cells, but the underlying mechanisms are unknown. Deletion of Rac1, a Rho guanosine triphosphatase, in adult mouse epidermis stimulated stem cells to divide and undergo terminal differentiation, leading to failure to maintain the interfollicular epidermis, hair follicles, and sebaceous glands. Rac1 exerts its effects in the epidermis by negatively regulating c-Myc through p21-activated kinase 2 (PAK2) phosphorylation. We conclude that a pleiotropic regulator of cell adhesion and the cytoskeleton plays a critical role in controlling exit from the stem cell niche and propose that Rac and Myc represent a global stem cell regulatory axis. 相似文献
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Murali-Krishna K Lau LL Sambhara S Lemonnier F Altman J Ahmed R 《Science (New York, N.Y.)》1999,286(5443):1377-1381
An understanding of how T cell memory is maintained is crucial for the rational design of vaccines. Memory T cells were shown to persist indefinitely in major histocompatibility complex (MHC) class I-deficient mice and retained the ability to make rapid cytokine responses upon reencounter with antigen. In addition, memory CD8 T cells, unlike na?ve cells, divided without MHC-T cell receptor interactions. This "homeostatic" proliferation is likely to be important in maintaining memory T cell numbers in the periphery. Thus, after na?ve CD8 T cells differentiate into memory cells, they evolve an MHC class I-independent "life-style" and do not require further stimulation with specific or cross-reactive antigen for their maintenance. 相似文献
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Li B Yu H Zheng W Voll R Na S Roberts AW Williams DA Davis RJ Ghosh S Flavell RA 《Science (New York, N.Y.)》2000,288(5474):2219-2222
T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression. 相似文献
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Lee KH Holdorf AD Dustin ML Chan AC Allen PM Shaw AS 《Science (New York, N.Y.)》2002,295(5559):1539-1542
The area of contact between a T cell and an antigen-presenting cell (APC) is known as the immunological synapse. Although its exact function is unknown, one model suggests that it allows for T cell receptor (TCR) clustering and for sustained signaling in T cells for many hours. Here we demonstrate that TCR-mediated tyrosine kinase signaling in na?ve T cells occurred primarily at the periphery of the synapse and was largely abated before mature immunological synapses had formed. These data suggest that many hours of TCR signaling are not required for T cell activation. These observations challenge current ideas about the role of immunological synapses in T cell activation. 相似文献
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In the course of the immune response against microbes, na?ve T cells proliferate and generate varied classes of effector cells, as well as memory cells with distinct properties and functions. Owing to recent technological advances, some of the most imposing questions regarding effector and memory T cell differentiation are now becoming experimentally soluble: How many classes of antigen-specific T cells exist, and how malleable are they in their fate and in their functional state? How might a spectrum of cell fates be imparted to the clonal descendants of a single lymphocyte? Where, when, and how does pathogen-associated information refine the instruction, selection, and direction of newly activated T cells as they perform their tasks in different locations and times? Some surprising new glimpses ahead on these subjects and other yet-unanswered questions are discussed. 相似文献
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The factors required for the generation of memory CD4 T cells remain unclear, and whether there is a continuing requirement for antigen stimulation is critical to design of vaccine strategies. CD4 effectors generated in vitro from na?ve CD4 T cells of mice efficiently gave rise to small resting memory cells after transfer to class II-deficient hosts, indicating no requirement for further antigen or class II recognition. 相似文献
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Gardner JM Devoss JJ Friedman RS Wong DJ Tan YX Zhou X Johannes KP Su MA Chang HY Krummel MF Anderson MS 《Science (New York, N.Y.)》2008,321(5890):843-847
The prevention of autoimmunity requires the elimination of self-reactive T cells during their development and maturation. The expression of diverse self-antigens by stromal cells in the thymus is essential to this process and depends, in part, on the activity of the autoimmune regulator (Aire) gene. Here we report the identification of extrathymic Aire-expressing cells (eTACs) resident within the secondary lymphoid organs. These stromally derived eTACs express a diverse array of distinct self-antigens and are capable of interacting with and deleting na?ve autoreactive T cells. Using two-photon microscopy, we observed stable antigen-specific interactions between eTACs and autoreactive T cells. We propose that such a secondary network of self-antigen-expressing stromal cells may help reinforce immune tolerance by preventing the maturation of autoreactive T cells that escape thymic negative selection. 相似文献
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CD8+ T cell cross-priming via transfer of proteasome substrates 总被引：1，自引：0，他引：1
Norbury CC Basta S Donohue KB Tscharke DC Princiotta MF Berglund P Gibbs J Bennink JR Yewdell JW 《Science (New York, N.Y.)》2004,304(5675):1318-1321
"Cross-priming" describes the activation of na?ve CD8+ T cells by professional antigen-presenting cells that have acquired viral or tumor antigens from "donor" cells. Antigen transfer is believed to be mediated by donor cell-derived molecular chaperones bearing short peptide ligands generated by proteasome degradation of protein antigens. We show here that cross-priming is based on the transfer of proteasome substrates rather than peptides. These findings are potentially important for the rational design of vaccines that elicit CD8+ T cell responses. 相似文献
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Rac基因是普遍存在于真核生物细胞中参与环境应急反应的重要基因。本文采用RT-PCR方法从哈茨木霉中成功克隆了哈茨木霉的Rac基因的eDNA,全长718bp,推测编码204个氨基酸,蛋白分子量为22.4kD。通过数据库检索等生物信息学方法分析发现哈茨木霉Rac与羊茅香柱菌相似性高达82％。与柄篮状菌相似性也达到75％。哈茨木霉Rac基因含有GTP／GDP结合和Effeetor区。Rac基因的cDNA序列及推测的氨基酸序列在GenBank上登录（登录号分别FJ595933和ACM24223）。 相似文献
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Human gammadelta T cells are considered to play a vital role in protective immunity through cytokine secretion and cytotoxic activity. We report that cells expressing the Vgamma2Vdelta2+-T cell receptor (Vdelta2+ T cells) also display principal characteristics of professional antigen-presenting cells such as dendritic cells. Thus, when activated, these cells efficiently processed and displayed antigens and provided co-stimulatory signals sufficient for strong induction of na?ve alphabeta T cell proliferation and differentiation. We suggest that, upon microbial activation, Vdelta2+ T cells participate in the induction of adaptive immune responses and that these cells may be a useful tool in vaccine development and immunotherapy. 相似文献