共查询到20条相似文献,搜索用时 15 毫秒
1.
Melhem NM Liu XD Boczkowski D Gilboa E Barratt-Boyes SM 《European journal of immunology》2007,37(8):2164-2173
A potentially powerful strategy for therapeutic HIV vaccination is the use of DC transfected with mRNA encoding autologous viral Ag, as epitopes presented by transfected DC would exactly reflect those expressed by infected cells in the individual. Using human and rhesus macaque monocyte-derived DC, we show that nucleofection is a superior method for mRNA transfection, resulting in high-level protein expression and DC maturation. DC transfected with SIV gag isolated from an infected monkey stimulated robust Ag-specific recall T cell responses of similar magnitude to those induced by peptide-pulsed PBMC that were predominantly CD8+ T cell mediated. Enhanced CD4+ T cell responses were stimulated when Gag was redirected into the lysosomal pathway via the targeting signal derived from lysosome-associated membrane protein-1 (LAMP-1). Rhesus DC transfected with lysosome-targeted gag encoding an escape mutation in an immunodominant CTL epitope stimulated CD4+ and CD8+ T cell responses of almost equivalent magnitude directed towards undefined epitopes outside of the mutated region. Finally, gag-transfected DC from SIV-infected monkeys stimulated significant Ag-specific recall T cell responses in an entirely autologous system. These findings demonstrate that mRNA-transfected DC expressing SIV Ag derived from infected monkeys stimulate broad and relevant T cell responses, supporting this approach for therapeutic HIV vaccine development. 相似文献
2.
Chen W Masterman KA Basta S Haeryfar SM Dimopoulos N Knowles B Bennink JR Yewdell JW 《European journal of immunology》2004,34(1):194-199
"Cross-priming" refers to the activation of naive CD8+ T cells by antigen-presenting cells that have acquired nominal antigens from another cell. The biological relevance of cross-priming of CD8+ T cells has recently been challenged (Zinkernagel, R. M., Eur. J. Immunol. 2002. 32: 2385-2392), on the basis that responses are weak or poorly quantitated, and the determinants recognized are undefined. Here we show that cross-priming is a robust process that elicits vigorous primary responses to multiple peptides in two well-defined systems. Our findings support the relevance of cross-priming in CD8+ T cell responses to viruses and tumor cells, and demonstrate that cross-priming elicits CD8+ T cells to determinants generated by the endogenous processing pathway. 相似文献
3.
Immune responses are by necessity highly regulated to achieve the appropriate balance of aggression and restraint. A mong
the many factors involved in maintaining this balance are the interactions between accessory molecule receptorse xpressed
on T cells and their ligands on antigen-presenting cells. Our studies during the past several years have focused on defining
how particular accessory molecule interactions influence the activation of naive CD4+ T cells and the subsequent development of effector function. In this article, we discuss our findings on the effects of distinct
accessory molecules with particular attention to the unique roles of LFA-1 and CD28 during different phases of the native
CD4+ cell response. 相似文献
4.
Evidence for CD4+ T cell responses common to Plasmodium falciparum and recall antigens 总被引:1,自引:0,他引:1
In individual donors which have never been exposed to malaria parasites,
the CD4+ T cell precursor frequencies for tetanus toxoid (TT) and
Plasmodium falciparum responses are similar (range 1:850- 1:4800). Limiting
dilution cultures set up in response to P. falciparum trophozoites can be
re-stimulated with the same stage of the parasite or TT and respond with
similar frequencies. A substantial overlap in the responses to different
agents was confirmed in suicide selection experiments where cells
responding to malaria parasite, TT or influenza virus antigens were deleted
using the cell cycle inhibitor cytosine arabinoside (Ara-C). The responses
of the remaining cells to P. falciparum were almost completely abrogated
and only weak responses were observed to different recall antigens (0.2-21%
of untreated control). Little or no effect was observed on the responses to
superantigen or mitogen. Furthermore, in contrast to superantigen, the
observed responses to TT and Plasmodium were polyclonal, the blastoid cells
generated reacting with a range of anti-TCR Vbeta antibodies with little
preferential usage.
相似文献
5.
Beverly J. Holmes Paul A. Macary Alistair Noble D. Michael Kemeny 《European journal of immunology》1997,27(10):2657-2665
There is a growing body of evidence which suggests that CD8+ T cells play an important part in regulating the IgE response to non-replicating antigens. In this study we have systematically investigated their role in the regulation of IgE and of CD4+ T cell responses to ovalbumin (OVA) by CD8+ T cell depletion in vivo. Following intraperitoneal immunization with alum-precipitated OVA, OVA-specific T cell responses were detected in the spleen and depletion of CD8+ T cells in vitro significantly enhanced the proliferative response to OVA. Depletion of CD8+ T cells in vivo 7 days after immunization failed to enhance IgE production, while depletion of CD8+ T cells on days 12–18 greatly enhanced the IgE response, which rose to 26 μ/ml following a second injection of anti-CD8 on day 35 and remained in excess of 1 μ/ml over 300 days afterwards. Reconstitution on day 21 of rats CD8-depleted on day 12 with purified CD8+ T cells from animals immunized on day 12 completely inhib ited the IgE response. This effect was antigen specific; CD8+ T cells from OVA-primed animals had little effect on the IgE response of bovine serum albumin immunized rats. In vivo, CD8+ T cell depletion decreased interferon (IFN)-γ production but enhanced interleukin (IL)-4 production by OVA-stimulated splenic CD4+ T cells. Furthermore, CD8+ T cell depletion and addition of anti-IFN-γ antibody enhanced IgE production in vitro in an IL-4-supplemented mixed lymphocyte reaction. These data clearly show that antigen-specific CD8+ T cells inhibit IgE in the immune response to non-replicating antigens. The data indicate two possible mechanisms: first, CD8+ T cells have direct inhibitory effects on switching to IgE in B cells and second, they inhibit OVA-specific IL-4 production but enhance IFN-γ production by CD4+ T cells. 相似文献
6.
CD4+CD25+ T cells as immunoregulatory T cells in vitro 总被引:7,自引:0,他引:7
Chai JG Tsang JY Lechler R Simpson E Dyson J Scott D 《European journal of immunology》2002,32(8):2365-2375
We have further characterized the in vitro phenotype and function of anergic and suppressive CD4(+)25(+) T cells. Following TCR ligation, DO.11.10 CD4(+)25(+) T cells suppress the activation of OT-1 CD8(+)25(-) T cells in an antigen nonspecific manner. Although suppression was seen when using a mixture of APC from both parental strains, it was very much more marked when using F1 APC. APC pretreated with, and then separated from CD4(+)25(+) T cells did not have diminished T cell costimulatory function, suggesting that APC are not the direct targets of CD4(+)25(+) T cell regulation. CTLA-4 blockade failed to abrogate suppression by CD4(+)25(+) T cells in mixing experiments. Although CD4(+)25(+) T cells failed to respond following cross-linking of TCR, they could be induced to proliferate following the addition of exogenous IL-2, allowing the generation of a T cell line from CD4(+)25(+) T cells. After the first in vitro restimulation, CD4(+)25(+) T cells were still anergic and suppressive following TCR engagement. However, after three rounds of restimulation, their anergic and suppressive status was abrogated. 相似文献
7.
Quiding-Järbrink M Lundin BS Lönroth H Svennerholm AM 《Clinical and experimental immunology》2001,123(1):81-87
In order to characterize T cell responses in human Helicobacter pylori infection, we have examined proliferative responses and cytokine production by CD4+ and CD8+ T cells isolated from duodenal ulcer patients and asymptomatic H. pylori carriers, after activation with some H. pylori antigens that may be important in disease development. For control purposes, T cells from uninfected volunteers were also examined. The different H. pylori antigens induced only modest proliferative responses in circulating CD4+ and CD8+ T cells from both H. pylori-infected and uninfected individuals. However, circulating T cells from H. pylori-infected subjects produced larger amounts of interferon-gamma (IFN-gamma) in response to the Helicobacter antigens than did T cells from uninfected volunteers. Furthermore, CD8+ T cells produced larger amounts of IFN-gamma than did CD4+ T cells, on a per cell basis. Most IFN-gamma-producing cells from both infected and uninfected volunteers appeared to be naive T cells expressing CD45RA. Increased production of IL-4 and IL-5 was, on the other hand, only seen in a few instances after stimulation of isolated CD4+ and CD8+ T cells. Stimulation of freshly isolated gastric T cells with the different H. pylori antigens did not result in increased proliferation or cytokine production. In conclusion, our results show that several different purified H. pylori antigens induce production of IFN-gamma, preferentially by CD8+ cells. Therefore, they suggest that IFN-gamma-secreting CD8+ cells contribute significantly to the cytokine response induced by H. pylori infection. 相似文献
8.
目的 探讨CD4^+CD25^+调节性T细胞是否对树突状细胞发挥免疫调节作用及其可能的机制。方法 用MACS(magnetic cell sorting)从BALB/c小鼠静息T细胞分离纯化CD4^+CD25^+T细胞,体外细胞增殖实验观察其对CD4^+CD25^+T细胞的免疫抑制作用;GM-CSF/IL-4培养自体小鼠骨髓来源DC,FACS(fluorescence-activated cell sorting)鉴定其表面分子特性;以CD3/CD28单克隆抗体活化CD4^+CD25^+调节性T细胞,FACS体外杀伤实验研究其对自体DC的调节作用,并观察穿孔素抑制剂EGTA对上述作用的影响。结果 用MACS法成功分离出CD4^+CD25^+T细胞,纯度可达98%,特异性表达而Faxp3基因,能明显抑制CD4^+CD25^+T细胞的体外增殖;骨髓来源的DC表达CDllc、MHCⅡ及少量协同刺激分子CD80、CD86;FACS体外杀伤实验证实以CD3/CD28抗体体外活化的CD4^+CD25^+调节性T细胞对自体DC有显著杀伤作用(P〈0.05),穿孔素抑制剂EGTA能部分抑制该杀伤效应(P〈0.05)。结论 CD4^+CD25^+调节性T细胞可通过杀伤作用对自体DC发挥免疫调节作用,穿孔素/颗粒酶杀伤途径可能参与其中。 相似文献
9.
CD4+ T cell matters in tumor immunity 总被引:6,自引:0,他引:6
CD4+ T cells have been shown to be able to affect tumor growth through both direct and indirect means. In addition, a requirement has been demonstrated for CD4+ T cells in the regulation and induction of T cell memory, and CD4+ suppressor T cells have been identified, stressing a role for CD4+ T cells in the induction and maintenance of antitumor immune responses. A review of the involvement of CD4+ T cells at different stages of tumor immunity is provided, and based on these data we discuss how CD4+ T cell response induction could be incorporated into tumor immunotherapy strategies. 相似文献
10.
Eddahri F Oldenhove G Denanglaire S Urbain J Leo O Andris F 《European journal of immunology》2006,36(4):855-863
CD4+ CD25+ T reg cells are critical for peripheral tolerance and prevention of autoimmunity. Here we show that CD4+ CD25+ T reg also regulate the magnitude of humoral responses against a panel of T-dependent antigens of foreign origin during both primary and secondary immune responses. Depletion of CD4+ CD25+ T cells leads to increased antigen-specific antibody production and affinity maturation but does not affect T-independent B cell responses, suggesting that CD4+ CD25+ T reg exert a feedback mechanism on non-self antigen-specific antibody secretion by dampening the T cell help for B cell activation. Moreover, we show that CD4+ CD25+ T reg also suppress in vitro B cell immunoglobulin production by inhibiting CD4+ CD25- T cell help delivery, and that blockade of TGF-beta activity abolishes this suppression. 相似文献
11.
Activation of thymic T cells by MHC alloantigen requires syngeneic, activated CD4+ T cells and B cells as APC 总被引:1,自引:0,他引:1
We examine here the in vitro requirements to activate immunocompetent T cells, present among thymocytes, to give rise to CTL, CD4+ T cells producing IL-2 and CD8+ T cells producing IFN-gamma. These thymocytes are naive in not having received antigen-dependent signals characteristic of the periphery. Their activation, upon stimulation with allogeneic spleen cells depleted of T cells, referred to here as allogeneic antigen-presenting cells (APCs), to produce allo-MHC-specific effector T cells, requires activated (radiation resistant) CD4+ T cells, syngeneic with the responding thymocytes. We refer here to these T cells as 'help'. Furthermore, optimal T cell activation requires an Ig+ B220+ cell in the allogeneic APC population, most probably a B cell. The allogeneic APCs cannot be replaced by conventional bone marrow (BM)-derived dendritic cells (DCs) activated by CD40 ligation or exposure to LPS. The requirements for both help and allogeneic B cells in the activation of thymocytes contrast with the requirements to generate substantial responses from splenic T cell populations. Activated, BM-derived DCs stimulate substantial splenic responses without help. These different requirements for activation could reflect the fact that thymocytes have not received an exit-thymus signal and/or that splenic T cells are heterogeneous, containing naive, memory and partially-activated T cells. 相似文献
12.
13.
CD4+ CD25+ FOXP3+ regulatory T cells from human thymus and cord blood suppress antigen-specific T cell responses 总被引:6,自引:0,他引:6
Activation of self-reactive T cells in healthy adults is prevented by the presence of autoantigen-specific CD4+CD25+ regulatory T cells (CD25+ Treg). To explore the functional development of autoantigen-reactive CD25+ Treg in humans we investigated if thymic CD25+ Treg from children aged 2 months to 11 years and cord blood CD25+ Treg are able to suppress proliferation and cytokine production induced by specific antigens. While CD4+CD25- thymocytes proliferated in response to myelin oligodendrocyte glycoprotein (MOG), tetanus toxoid and beta-lactoglobulin, suppression of proliferation was not detected after the addition of thymic CD25+ Treg. However, CD25+ Treg inhibited interferon (IFN)-gamma production induced by MOG, which indicates that MOG-reactive CD25+ Treg are present in the thymus. In contrast, cord blood CD25+ Treg suppressed both proliferation and cytokine production induced by MOG. Both cord blood and thymic CD25+ Treg expressed FOXP3 mRNA. However, FOXP3 expression was lower in cord blood than in thymic CD25+ T cells. Further characterization of cord blood CD25+ T cells revealed that FOXP3 was highly expressed by CD25+CD45RA+ cells while CD25+CD45RA- cells contained twofold less FOXP3, which may explain the lower expression level of FOXP3 in cord blood CD25+ T cells compared to thymic CD25+ T cells. In conclusion, our data demonstrate that low numbers of MOG-reactive functional CD25+ Treg are present in normal thymus, but that the suppressive ability of the cells is broader in cord blood. This suggests that the CD25+ Treg may be further matured in the periphery after being exported from the thymus. 相似文献
14.
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16.
Isogai S Jedrzkiewicz S Taha R Hamid Q Martin JG 《The Journal of allergy and clinical immunology》2005,115(3):521-526
BACKGROUND: The role of CD8+ T cells in the immune response to airway challenge with an allergen is poorly understood. OBJECTIVE: The aim of this study was to test the hypothesis that resident naive CD8+ T cells modulate the magnitude of CD4+ T cell-dependent allergic airway responses. METHODS: Cervical lymph node CD4+ T cells (2 x 10(6)) were harvested from ovalbumin (OVA)- or sham-sensitized rats and injected intraperitoneally into naive Brown Norway recipients. The recipients were treated with a CD8alpha mAb (OX-8) to deplete the resident CD8+ T cells (n = 12) or mouse ascites (n = 12). Two days after adoptive transfer, the recipient animals were OVA challenged, lung resistance was measured for 8 hours, and bronchoalveolar lavage (BAL) was performed. RESULTS: After OVA challenge, primed CD4-transferred CD8-depleted rats had larger early airway responses and late airway responses compared with primed CD4-transferred CD8-nondepleted rats (early airway responses: 158.6% +/- 19.2% vs 115.7% +/- 5.9%, P < .05; late airway responses: 8.5% +/- 1.7% vs 4.4% +/- 0.9%, P < .05). BAL eosinophilia was also greater (4.67% +/- 0.45% vs 2.34 +/- 0.26%, P < .01). The cells in BAL fluid expressing IL-4 mRNA were not significantly changed by CD8 depletion, but IL-5 mRNA+ cells were higher in number, and IFN-gamma mRNA+ cells were fewer in the CD8-depleted group. CONCLUSIONS: Resident CD8+ T cells downregulate the late allergic response and airway inflammation evoked by CD4+ T-cell transfers in Brown Norway rats. This downregulation does not require antigen priming. 相似文献
17.
Nagorsen D Scheibenbogen C Letsch A Germer CT Buhr HJ Hegewisch-Becker S Rivoltini L Thiel E Keilholz U 《Journal of translational medicine》2005,3(1):3
Introduction
Spontaneous T cell responses against specific tumor-associated antigens (TAA) are frequently detected in peripheral blood of tumor patients of various histiotypes. However, little is known about whether these circulating, spontaneously occurring, TAA-reactive T cells influence the clinical course of disease. 相似文献18.
Mendiratta SK Kovalik JP Hong S Singh N Martin WD Van Kaer L 《International immunology》1999,11(3):351-360
Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class II-peptide complex, H2-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion. 相似文献
19.
Kawaguchi S Wada T Ida K Sato Y Nagoya S Tsukahara T Kimura S Sahara H Ikeda H Shimozawa K Asanuma H Torigoe T Hiraga H Ishii T Tatezaki SI Sato N Yamashita T 《Journal of translational medicine》2005,3(1):1-9
BACKGROUND: Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18), and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. METHODS: A 9-mer peptide (SYT-SSX B: GYDQIMPKK) spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i) who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive), (ii) HLA-A*2402 positive, (iii) between 20 and 70 years old, (iv) ECOG performance status between 0 and 3, and (v) who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg) were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. RESULTS: A total of 16 vaccinations were carried out in six patients. The results were (i) no serious adverse effects or DTH reactions, (ii) suppression of tumor progression in one patient, (iii) increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv) successful induction of peptide-specific CTLs from four patients. CONCLUSIONS: Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy. 相似文献
20.
Whitmire JK 《Virology》2011,411(2):216-228
CD4+ T cells - often referred to as T-helper cells - play a central role in immune defense and pathogenesis. Virus infections and vaccines stimulate and expand populations of antigen-specific CD4+ T cells in mice and in man. These virus-specific CD4+ T cells are extremely important in antiviral protection: deficiencies in CD4+ T cells are associated with virus reactivation, generalized susceptibility to opportunistic infections, and poor vaccine efficacy. As described below, CD4+ T cells influence effector and memory CD8+ T cell responses, humoral immunity, and the antimicrobial activity of macrophages and are involved in recruiting cells to sites of infection. This review summarizes a few key points about the dynamics of the CD4+ T cell response to virus infection, the positive role of pro-inflammatory cytokines in the differentiation of virus-specific CD4+ T cells, and new areas of investigation to improve vaccines against virus infection. 相似文献