共查询到20条相似文献,搜索用时 15 毫秒
1.
Hiroyuki Sugimoto Tomoki ItoYoshitaro Torii Hideki AmuroTakashi Yokoi Tsutomu TanijiriRie Miyamoto Naoko MurakamiRyuichi Amakawa Shirou Fukuhara 《Clinical immunology (Orlando, Fla.)》2010,136(2):205-216
Although Bacillus Calmette–Guérin (BCG) has historically emerged as a potent adjuvant in cancer immunization through dendritic cell (DC) activation, the efficacy of its antitumor effect has been limited. Therefore, the strategy of adjuvant therapy using BCG needs to be improved by adding enhancers. Here we found that thymic stromal lymphopoietin (TSLP) acts as an enhancer for the BCG-mediated antitumor effect. While BCG-stimulated DCs induced CD8+ T cell production of IFN-γ without strong cell expansion, TSLP-stimulated DCs induced robust CD8+ T cell expansion without high quantities of IFN-γ production. Notably, DCs stimulated with both BCG and TSLP induced robust expansion of CD8+ T cells that produced a large amount of IFN-γ with a potent cytolytic activity related to granzyme B expression. Our data suggest that TSLP is a good adjuvant to enhance the BCG-mediated cytotoxic T cell effect through DC activation, and provide a functional basis for a novel strategy for antitumor immune-based therapy. 相似文献
2.
Sommer Frank; Huber Magdalena; Rollinghoff Martin; Lohoff Michael 《International immunology》1995,7(11):1779-1786
The murine CD44 receptor family is thought to be involved ina variety of lymphocyte functions, including lymphopoesis, lymphocytehoming and cell migration. Herein, we show that murine CD44also plays a role as a co-stimulatory molecule for the activationof CD4+ T cells. Ligation of CD44 by mAb enhanced IL-2 productionof long-term cultured, anti-CD3-stimulated Th1 cell lines. Moreover,anti-CD44 mAb synergized with anti-CD28 mAb in exerting thiseffect. A synergism of anti-CD28 and anti-CD44 mAb to co-stimulateIL-2 production was also observed in anti-CD3- triggered, freshlyisolated splenic CD4+ T cells. Blocking experiments with cyclosporinA indicated that the intracellular pathways used by the CD28and CD44 molecules appear to be different. In contrast to theeffects on the IL-2 production of Th1 cells, neither anti-CD44mAb alone nor the combination of anti-CD44 with anti-CD28 wereable to induce proliferation of anti-CD3-triggered Th1 cells.In accordance, triggering of CD44 and/or CD28 by mAb was notsufficient to reverse the previously described proliferativeblock. This term describes the unresponsiveness of Th1cells against IL-2, which occurs when Th1 cells are triggeredby anti-CD3 in the absence of co-signals. These data lead usto propose a model of Th1 cell activation which includes twofunctionally different types of co-signals: one for IL-2 productionand a separate one for proliferation. 相似文献
3.
Expression of the CD8 alpha alpha homodimer has been used to differentiate lymphoid (CD8alpha(+)) from myeloid (CD8alpha(-)) dendritic cells (DCs). We have reported that CD8alpha(+) and CD8alpha(-) DCs have differential abilities to stimulate proliferation in allogeneic T cells. However, no specific function has been attributed to DC-derived CD8alpha. The current study examines the hypothesis that CD8 alpha alpha expression on DCs regulates DC-induced T cell activation. CD8alpha(-) transduced bone marrow-derived DCs were more potent stimulators of T cell proliferation, and produced significantly greater quantities of IL-12 in co-culture with T cells. LCK, a kinase whose expression is reported to be T cell-restricted and known to bind to the cytoplasmic tail of CD8 alpha beta in T cells, was detected readily in primary CD8alpha(+) splenic DCs and at greater levels than CD8alpha(-) DCs from the same tissues. LCK also co-precipitated with CD8alpha on immunblots strongly suggesting its role in CD8alpha(+) DC-induced T cell activation. Collectively, these data show that CD8alpha expressed on DC may not only be a lineage/maturation marker but also contribute to DC function. 相似文献
4.
免疫突触与T细胞活化 总被引:2,自引:1,他引:2
淋巴细胞活化是适应性免疫应答的关键因素,免疫突触的形成是T细胞识别抗原、增殖和活化的关键步骤,是机体细胞免疫应答和体液免疫应答的重要组成部分.干预免疫突触形成,可望用于预防治疗与免疫相关的疾病. 相似文献
5.
Gomez TS Hamann MJ McCarney S Savoy DN Lubking CM Heldebrant MP Labno CM McKean DJ McNiven MA Burkhardt JK Billadeau DD 《Nature immunology》2005,6(3):261-270
Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalization but considerably affected T cell receptor-stimulated T cell activation by regulating multiple biochemical signaling pathways and the accumulation of F-actin at the immunological synapse. Moreover, Dyn2 interacted directly with the Rho family guanine nucleotide exchange factor Vav1, and this interaction was required for T cell activation. These data identify a functionally important interaction between Dyn2 and Vav1 that regulates actin reorganization and multiple signaling pathways in T lymphocytes. 相似文献
6.
Goldstein JS Chen T Gubina E Pastor RW Kozlowski S 《European journal of immunology》2000,30(11):3266-3270
In addition to the TCR-ligand interaction, other receptor-ligand pairs, such as LFA-1 and ICAM-1, play a major role in the activation of T cells. Recent studies of T cell activation suggest a coordinated movement of LFA-1 and ICAM-1 in forming a defined zone in the immunological synapse. It is unclear from these studies whether the organized molecular geometry of the immunological synapse is necessary for ICAM-1 enhancement of T cell activation. In this report, we demonstrate that ICAM-1 can enhance the activation of CD8(+) T cells by MHC-peptide in the absence of an organized immunologic synapse. Therefore, although the molecular organization of the immunologic synapse may amplify stimuli, it is not an absolute requirement for either CD8(+) T cell activation or the ICAM-1 enhancement of TCR activation. 相似文献
7.
8.
C Termeer H Johannsen T Braun A Renkl T Ahrens R W Denfeld M B Lappin J M Weiss J C Simon 《Journal of leukocyte biology》2001,70(5):715-722
The interaction between CD40 on dendritic cells (DC) and its ligand CD154 has been recognized to be an important feature in the maturation of DC. Here, we were interested in the role of CD44 a surface receptor shown to mediate cell-cell adhesion and binding to Hyaluronic acid (HA). Western blot analysis of human DC stimulated for 3-12 h with CD154 revealed the rapid induction of the 85 kDa standard form of CD44 and an increased HA-binding affinity. Time-lapse video-imaging microscopy of human DC co-cultured on CD154-transfected murine fibroblasts showed that the CD44 up-regulation coincided with the rapid induction of homotypic DC clustering, which did not occur on empty vector-transfected fibroblasts. In this system, addition of anti-CD44s mAbs abrogated DC-cluster formation, thereby inhibiting further maturation, as shown by a reduced TNF-alpha production and inhibition of CD154-induced MHC class II up-regulation. However, co-incubation with HA-degrading enzymes induced no changes in the CD154-mediated DC clustering and maturation. 相似文献
9.
Brossard C Feuillet V Schmitt A Randriamampita C Romao M Raposo G Trautmann A 《European journal of immunology》2005,35(6):1741-1753
The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free synapses present a number of tight appositions (cleft size approximately 15 nm), all along the synapse. These tight appositions cover a significantly larger surface fraction of antigen-dependent synapses. In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap. A similar distribution is observed for PKCtheta and talin. A concentric organization characteristic of prototypical synapses is rarely observed, even when dendritic cells are paralyzed by cytoskeletal poisons. In T-DC synapses, the interaction surface is composed of several tens of submicronic contact spots, with no large-scale segregation of CD3 and LFA-1. As a comparison, in T-B synapses, a central cluster of CD3 is frequently observed by immunofluorescence, and electron microscopy reveals a central tight apposition. Our data show that it is inappropriate to consider the concentric structure as a "mature synapse" and multifocal structures as immature. 相似文献
10.
We have identified a new T cell activation pathway mediated by the lymphocyte homing receptor/CD44 molecule, 8B2.5, a local monoclonal antibody (mAb), which recognizes two glycoproteins of 85 and 220 kDa with wide tissue distribution, is shown by sequential immunoprecipitations and competitive antibody-binding inhibition experiments with several CD44 reference mAb to recognize the CD44 molecule. The 8B2.5 mAb, but not reference CD44 mAb, is able to induce resting peripheral blood lymphocytes to proliferate in the presence of phorbol esters. This proliferation is monocyte dependent but Fc independent and results from 8B2.5 mAb binding to CD44 molecules both expressed by both T cells and monocytes. In the absence of monocytes, proliferation can be restored by solid-phase 8B2.5 mAb, or, to a lesser extent, by adding interleukin 2. Although CD3 and CD44 surface molecules are found physically independent, T cell activation via the CD44 pathway is inhibited by CD3 modulation. In addition to the direct role of CD44 molecules in T cell proliferation, CD44 mAb can up- or- down-regulate the CD3 and CD28 pathways, depending on the presence of monocytes. These results suggest that T cell and monocyte binding to high endothelial venule or extracellular matrix proteins could further promote clonal expansion of resting T cells migrating in certain specific anatomic sites. 相似文献
11.
The role of CD44 in T cell biology remains incompletely understood. Although studies using anti-CD44 antibodies have implicated this cell adhesion molecule in a variety of important T cell processes, few T cell defects have been reported in CD44-deficient mice. We have assessed the requirement for CD44 in T cell development and mature T cell function by analyzing mice in which CD44(-/-) and WT cells were produced simultaneously. In mixed (CD44(-/-) + CD44(+/+)) bone marrow chimeras, production of CD44(-/-) T cells was shown to be reduced compared to WT cells due to inefficient intrathymic development. In addition, mature CD44(-/-) CD8(+) T cells generated a substantially lower response than WT T cells after infection of mice with lymphocytic choriomeningitis virus, with the reduction in response apparent in both lymphoid and non-lymphoid tissues. Overall, these results demonstrate a poor capacity of CD44(-/-) T lineage cells to compete with WT cells at multiple levels, implicating CD44 in normal T cell function. 相似文献
12.
13.
Kohlmeier JE Miller SC Smith J Lu B Gerard C Cookenham T Roberts AD Woodland DL 《Immunity》2008,29(1):101-113
Innate recognition of invading pathogens in peripheral tissues results in the recruitment of circulating memory CD8(+) T cells to sites of localized inflammation during the early phase of a recall response. However, the mechanisms that control the rapid recruitment of these cells to peripheral sites are poorly understood, particularly in relation to influenza and parainfluenza infections of the respiratory tract. In this study, we demonstrate a crucial role for C-C chemokine receptor 5 (CCR5) in the accelerated recruitment of memory CD8(+) T cells to the lung airways during virus challenge. Most importantly, CCR5 deficiency resulted in decreased recruitment of memory T cells expressing key effector molecules and impaired control of virus replication during the initial stages of a secondary response. These data highlight the critical importance of early memory T cell recruitment for the efficacy of cellular immunity in the lung. 相似文献
14.
Li QJ Dinner AR Qi S Irvine DJ Huppa JB Davis MM Chakraborty AK 《Nature immunology》2004,5(8):791-799
How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. Here we present evidence that CD4 affects the responsiveness of T helper cells by controlling spatial localization of the tyrosine kinase Lck in the synapse. This finding, as well as further in silico and in vitro experiments, led us to develop a molecular model in which endogenous and agonist pMHC molecules act cooperatively to amplify T cell receptor signaling. At the same time, activation due to endogenous pMHC molecules alone is inhibited. A key feature is that the binding of agonist pMHC molecules to the T cell receptor results in CD4-mediated spatial localization of Lck, which in turn enables endogenous pMHC molecules to trigger many T cell receptors. We also discuss broader implications for T cell biology, including thymic selection, diversity of the repertoire of self pMHC molecules and serial triggering. 相似文献
15.
Morishita M Uchimaru K Sato K Ohtsuru A Yamashita S Kanematsu T Yamashita N 《International journal of molecular medicine》2004,13(1):33-39
Although thyroglobulin (Tg) would be expected to act as a tumor-associated antigen that might be exploitable by immunotherapy against thyroid cancers, it remains unclear how to effectively enhance the immune response to Tg in human since it is a self-component glycoprotein. We therefore tested whether and how human peripheral blood (PB) monocyte-derived dendritic cells (DCs) pulsed with human (h)Tg would induce activation of hTg-specific T cells. We found that immature DCs (iDCs) exhibited a higher endocytic capacity for fluorescein isothiocyanate-conjugated hTg than did mature DCs (mDCs). Although freshly isolated T cells responded poorly to mDCs, hTg-primed T cells responded much more strongly to hTg pulsed mDCs, which selectively induced IFN-gamma-secreting T cells. These results suggest that hTg-pulsed mDCs enhance the responses of Tg-specific T cells, raising the possibility that vaccination with hTg-pulsed mDCs may be an effective approach as immunotherapy to potentiate thyroid cancer specific therapy. 相似文献
16.
To investigate the signaling function of the Src-family protein tyrosine kinase Lck in mature T cells, we generated transgenic mice that expressed Lck in thymocytes but not in peripheral lymphocytes. We compared the phenotype and signaling capacity of Lck-deficient T cells with T cells from mice expressing a dominant inhibitory form of Lck and found that both mouse strains have diminished numbers of mature CD8(+) T cells and respond poorly to CD28 costimulation. However, while T cells that lack Lck fail to mobilize Ca(2+) after stimulation, those expressing the dominant negative protein do so normally. Our data demonstrate that Lck plays several unique roles in mature lymphocyte signaling. 相似文献
17.
《Advances in medical sciences》2022,67(2):353-363
Antigen recognition and presentation are highlighted as the first steps in developing specialized antigen responses. Dendritic cells (DCs) are outstanding professional antigen-presenting cells (APCs) responsible for priming cellular immunity in pathological states, including cancer. However, the diminished or repressed function of DCs is thought to be a substantial mechanism through which tumors escape from the immune system. In this regard, DCs obtained from breast cancer (BC) patients represent a notably weakened potency to encourage specific T-cell responses. Additionally, impaired DC-T-cell cross-talk in BC facilitates the immune evade of cancer cells and is connected with tumor advancement, immune tolerance, and adverse prognosis for patients. In this review we aim to highlight the available knowledge on DC-T-cell interactions in BC aggressiveness and show its therapeutic potential in BC treatment. 相似文献
18.
目的:建立T细胞受体(TCR)在免疫突触形成过程中作重定向(reorientation)运动的机制模型.方法:基于经典流体力学环境中的双分子反应传能原理,提出了T细胞受体的涡旋驱动模型,利用免疫突触内耦合的受体或配体分子作为涡源驱动T细胞受体分子的募集.结果:模型计算的结果表明,在强度及作用频率同时具备一定范围的涡旋连续驱动下,TCR重定向运动速度可达到实验测定的范围(0.04~0.1 μm/s).结论:本模型证明突触内受体/配体对耦合时通过将其结合自由能转化为细胞内外流体涡旋运动的机械能可能直接提供了TCR重定向运动的驱动力. 相似文献
19.
Although the T cell costimulatory molecules CD2 and CD28 are enriched within the immunological synapse (IS), it has been suggested that costimulatory molecules need not be localized to the contact site between a T cell and an antigen-presenting cell (APC) in order to costimulate T cell activation. To determine whether CD2 or CD28 engagement outside of the IS is sufficient to costimulate T cell activation, we compared mouse T cell responses to anti-CD3 and anti-CD2 monoclonal antibodies (mAbs) or anti-CD3 and anti-CD28 mAbs immobilized on the same, i.e., in cis, or on different, i.e., in trans, 10 micron polystyrene microspheres. In comparison to T cells that were stimulated with co-immobilized anti-CD3 and anti-CD2 or anti-CD28 mAbs, DNA synthesis, interleukin (IL)-2 production, and cellular proliferation were all severely impaired following T cell stimulation with anti-CD3 and anti-CD2 mAbs or anti-CD3 and anti-CD28 mAbs on different microspheres. Deficient cellular proliferation and IL-2 synthesis by T cells that experienced CD3 and CD2 or CD28 cross-linking in trans provides evidence that costimulatory molecules must function in the context of the IS for optimal T cell activation. 相似文献
20.
Kim IS Song YM Cho TH Pan H Lee TH Kim SJ Hwang SJ 《Tissue engineering. Part A》2011,17(9-10):1327-1340
Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of Schwann cells via the induction of neurotrophic factor release and guide-increased axonal outgrowth in vivo. The effectiveness of long-term ES highlights the feasibility of a BEC-based therapeutic device to accelerate nerve regeneration of severed peripheral nerve injuries with a gap. 相似文献