共查询到20条相似文献,搜索用时 15 毫秒
1.
Irena Adkins Jana Kamanova Aneta Kocourkova Martina Svedova Jakub Tomala Hana Janova Jiri Masin Barbora Chladkova Ladislav Bumba Marek Kovar Padraig J. Ross Ludmila Tuckova Radek Spisek Kingston H. G. Mills Peter Sebo 《PloS one》2014,9(8)
Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The toxin targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In the present study, we analyzed the modulatory effects of CyaA on adhesive, migratory and antigen presenting properties of Toll-like receptor (TLR)-activated murine and human dendritic cells (DCs). cAMP signaling of CyaA enhanced TLR-induced dissolution of cell adhesive contacts and migration of DCs towards the lymph node-homing chemokines CCL19 and CCL21 in vitro. Moreover, we examined in detail the capacity of toxin-treated DCs to induce CD4+ and CD8+ T cell responses. Exposure to CyaA decreased the capacity of LPS-stimulated DCs to present soluble protein antigen to CD4+ T cells independently of modulation of co-stimulatory molecules and cytokine production, and enhanced their capacity to promote CD4+CD25+Foxp3+ T regulatory cells in vitro. In addition, CyaA decreased the capacity of LPS-stimulated DCs to induce CD8+ T cell proliferation and limited the induction of IFN-γ producing CD8+ T cells while enhancing IL-10 and IL-17-production. These results indicate that through activation of cAMP signaling, the CyaA may be mobilizing DCs impaired in T cell stimulatory capacity and arrival of such DCs into draining lymph nodes may than contribute to delay and subversion of host immune responses during B. pertussis infection. 相似文献
2.
Adriana Osickova Jiri Masin Catherine Fayolle Jan Krusek Marek Basler Eva Pospisilova Claude Leclerc Radim Osicka Peter Sebo 《Molecular microbiology》2010,75(6):1550-1562
The adenylate cyclase toxin‐haemolysin of Bordetella (CyaA) targets CD11b+ myeloid phagocytes and translocates across their cytoplasmic membrane an adenylate cyclase (AC) enzyme that catalyses conversion of cytosolic ATP into cAMP. In parallel, CyaA acts as a cytolysin forming cation‐selective pores, which permeabilize cell membrane and eventually provoke cell lysis. Using cytolytic activity, potassium efflux and patch‐clamp assays, we show that a combination of substitutions within the pore‐forming (E570Q) and acylation‐bearing domain (K860R) ablates selectively the cell‐permeabilizing activity of CyaA. At the same time, however, the capacity of such mutant CyaA to translocate the AC domain across cytoplasmic membrane into cytosol of macrophage cells and to elevate cellular cAMP concentrations remained intact. Moreover, the combination of E570Q+K860R substitutions suppressed the residual cytolytic activity of the enzymatically inactive CyaA/OVA/AC‐ toxoid on CD11b‐expressing monocytes, while leaving unaffected the capacity of the mutant toxoid to deliver in vitro a reporter CD8+ T cell epitope from ovalbumin (OVA) to the cytosolic pathway of dendritic cells for MHC class I‐restricted presentation and induce in vivo an OVA‐specific cytotoxic T cell response. CyaA, hence, employs a mechanism of AC enzyme domain translocation across cellular membrane that avoids passage across the cytolytic pore formed by toxin oligomers. 相似文献
3.
Zloza A Jagoda MC Lyons GE Graves MC Kohlhapp FJ O'Sullivan JA Lacek AT Nishimura MI Guevara-Patiño JA 《Cancer immunology, immunotherapy : CII》2011,60(2):291-297
CD8+ T cell function depends on a finely orchestrated balance of activation/suppression signals. While the stimulatory role of
the CD8 co-receptor and pleiotropic capabilities of TGF-β have been studied individually, the influence of CD8 co-receptor
on TGF-β function in CD8+ T cells is unknown. Here, we show that while CD8 enhances T cell activation, it also enhances susceptibility to TGF-β-mediated
immune suppression. Using Jurkat cells expressing a full-length, truncated or no αβCD8 molecule, we demonstrate that cells
expressing full-length αβCD8 were highly susceptible, αβCD8-truncated cells were partially susceptible, and CD8-deficient
cells were completely resistant to suppression by TGF-β. Additionally, we determined that inhibition of Lck rendered mouse
CD8+ T cells highly resistant to TGF-β suppression. Resistance was not associated with TGF-β receptor expression but did correlate
with decreased Smad3 and increased Smad7 levels. These findings highlight a previously unrecognized third role for CD8 co-receptor
which appears to prepare activated CD8+ T cells for response to TGF-β. Based on the important role which TGF-β-mediated suppression plays in tumor immunology, these
findings unveil necessary considerations in formulation of CD8+ T cell-related cancer immunotherapy strategies. 相似文献
4.
Maria Grazia Cusi Barbara Martorelli Giuseppa Di Genova Chiara Terrosi Giuseppe Campoccia Pierpaolo Correale 《Immunity & ageing : I & A》2010,7(1):14
Respiratory syncytial virus (RSV) is the major pathogen causing respiratory disease in young infants and it is an important
cause of serious illness in the elderly since the infection provides limited immune protection against reinfection. In order
to explain this phenomenon, we investigated whether healthy adults of different age (20-40; 41-60 and > 60 years), have differences
in central and effector memory, RSV-specific CD8+ T cell memory immune response and regulatory T cell expression status. In
the peripheral blood of these donors, we were unable to detect any age related difference in term of central (CD45RA-CCR7+) and effector (CD45RA-CCR7-) memory T cell frequency. On the contrary, we found a significant increase in immunosuppressive regulatory (CD4+25+FoxP3+) T cells (Treg) in the elderly. An immunocytofluorimetric RSV pentamer analysis performed on these donors' peripheral blood mononuclear
cells (PBMCs), in vitro sensitized against RSV antigen, revealed a marked decline in long-lasting RSV specific CD8+ memory T cell precursors expressing
interleukin 7 receptor α (IL-7Rα), in the elderly. This effect was paralleled by a progressive switch from a Th1 (IFN-γ and
TNF-α) to a Th2 (IL-10) functional phenotype. On the contrary, an increase in Treg was observed with aging. The finding of Treg over-expression status, a prominent Th2 response and an inefficient RSV-specific effector memory CD8+ T cell expansion in
older donors could explain the poor protection against RSV reinfection and the increased risk to develop an RSV-related severe
illness in this population. Our finding also lays the basis for new therapeutic perspectives that could limit or prevent severe
RSV infection in elderly. 相似文献
5.
Guilian Yang Chunfeng Wang Fengqi Hao Dan Zhao Yunlong Zhang Yu Li 《Parasitology international》2010,59(4):517-523
Eimeria spp. are the causative agents of coccidiosis, a major disease affecting the poultry industry. A recombinant non-antibiotic Escherichia coli that expresses the Eimeria tenella SO7 gene was constructed and its protective efficacy against homologous infection in chickens was determined. The three-day-old chickens were orally immunized with the recombinant non-antibiotic SO7 gene expressing E. coli and boosted two weeks later. Four weeks after the second immunization, the chickens were challenged with 5 × 104 homologous sporulated oocysts. The protective effects of the recombinant non-antibiotic E. coli were determined by measuring body weight change, mortality, histopathology, lesion scores, oocyst counts, the specific antibody response and the frequency of CD4+ and CD8+ lymphocytes in peripheral blood. The results showed that immunization with SO7 expressing E. coli resulted in significantly improved body weight gain, reduced lesion scores and oocyst shedding in immunized chickens compared to controls. Furthermore, administration of recombinant SO7 expressing E. coli leads to a significant increase in serum antibody, CD4+ and CD8+ T cells in peripheral blood of chickens. These results, therefore, suggest that the recombinant non-antibiotic E. coli that expresses the SO7 gene is able to effectively stimulate host protective immunity as evidenced by the induction of development of both humoral and cell-mediated immune responses against homologous challenge in chickens. 相似文献
6.
Vinicius C. Santana Mariana O. Diniz Francisco A. M. O. Cariri Armando M. Ventura Edécio Cunha-Neto Rafael R. Almeida Marco A. Campos Graciela K. Lima Luís C. S. Ferreira 《PloS one》2013,8(8)
Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8+ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8+ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses. 相似文献
7.
As a vaccine vector, Listeria monocytogenes targets the innate immune system, resulting in a cytokine response that enhances antigen-presenting cell function as well as inducing a Th1 profile. It also enhances cell-mediated immunity by targeting antigen delivery in antigen-presenting cells to both the MHC class I pathway of exogenous presentation that activates CD8 T cells and the MHC class II pathway that processes antigen endogenously and presents it to CD4 T cells. In this review, we describe the development of vaccine constructs that target the human papillomavirus 16 (HPV-16) E7 antigen, and we characterize their effects on tumor regression as well as various immune parameters both innate and adaptive. In particular, we describe the effect on tumor angiogenesis, induction of antitumor suppressor factors like CD4+CD25+ T cells and regulatory cytokines TGF- and IL-10, homing and infiltration of antigen-specific CD8+ T cells to the tumor, and also effects of the vaccines on antigen-presenting cells, especially focusing on dendritic cell maturation and ability to influence tumor regression. We believe that the identification of several immune parameters that correlate with antitumor efficacy, and of some that have a negative correlation, may have wider application for other cancer immunotherapeutic approaches.This article is a symposium paper from the second international conference Strategies for Immune Therapy, 29 February–3 March 2004, Würzburg, Germany; summarized by G. Pawelec and C. Gouttefangeas. 相似文献
8.
Monica Vaccari Rabih Halwani L. Jean Patterson Adriano Boasso Jennifer Beal Elzbieta Tryniszewska Anna Hryniewicz David Venzon Elias K. Haddad Mohamed El-Far Margherita Rosati George N. Pavlakis Barbara K. Felber Saleh Al-Muhsen Marjorie Robert-Guroff Rafick-Pierre Sekaly Genoveffa Franchini 《Journal of virology》2013,87(6):3526-3537
We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4+ and CD8+ T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV gag, pol, env, and Retanef genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV gag and nef genes but not Retanef or env (1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8+CM9+ effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8+ T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8+ T-cell responses. 相似文献
9.
Cheng WH Holmstrom A Li X Wu RT Zeng H Xiao Z 《Biological trace element research》2012,146(2):230-235
Selenium (Se) is known to regulate tumorigenesis and immunity at the nutritional and supranutritional levels. Because the
immune system provides critical defenses against cancer and the athymic, immune-deficient NU/J nude mice are known to gradually
develop CD8+ and CD4+ T cells, we investigated whether B and T cell maturation could be modulated by dietary Se and by tumorigenesis in nude mice.
Fifteen homozygous nude mice were fed a Se-deficient, Torula yeast basal diet alone (Se−) or supplemented with 0.15 (Se+)
or 1.0 (Se++) mg Se/kg (as Na2SeO4) for 6 months, followed by a 7-week time course of PC-3 prostate cancer cell xenograft (2 × 106 cells/site, 2 sites/mouse). Here, we show that peripheral B cell levels decreased in nude mice fed the Se − or Se++ diet
and the CD4+ T cell levels increased in mice fed the Se++ diet. During the PC-3 cell tumorigenesis, dietary Se status did not affect peripheral
CD4+ or CD8+ T cells in nude mice whereas mice fed with the Se++ diet appeared to exhibit greater peripheral CD25+CD4+ T cells on day 9. Dietary Se status did not affect spleen weight in nude mice 7 weeks after the xenograft. Spleen weight
was associated with frequency of peripheral CD4+, but not CD8+ T cells. Taken together, dietary Se at the nutritional and supranutritional levels regulates peripheral B and T cells in
adult nude mice before and after xenograft with PC-3 prostate cancer cells. 相似文献
10.
Jiang Yunbo Fang Liurong Xiao Shaobo Zhang Hui Chen Huanchun 《Frontiers of Biology in China》2007,2(1):85-91
Pseudorabies virus (PRV), an alpha-herpesvirus, has been developed as a live viral vector for animal vaccines. However, the
PRV recombinant virus TK−/gE−/GP5+ expressing GP5 of porcine reproductive and respiratory syndrome virus (PRRSV), based on the PRV genetically depleted vaccine
strain TK−/gE−/LacZ+, scarcely stimulated the vaccinated animals to produce neutralizing antibodies against PRRSV. To develop a booster-specific
immune response of such PRV recombinants, the ORF5m gene (the modified ORF5 gene having better immune responses) was substituted for the ORF5 gene and introduced into PRV TK−/gE−/LacZ+, resulting in a PRV recombinant named TK−/gE−/GP5m+, which expressed the modified GP5m protein. The recombinant virus was confirmed using PCR, Southern blotting and Western
blotting. TK−/gE−/GP5m+ and TK−/gE−/GP5+ expressing the authentic GP5 protein were inoculated into Balb/c mice to evaluate their immune responses. The results indicated
that the protecting neutralization antibodies (the 3/6 vaccinated mice obtained 1:16) and cell immune responses induced by
TK−/gE−/GP5m+ against PRRSV were higher than that induced by TK−/gE−/GP5+. Thus, the development of the new PRV recombinant expressing the modified GP5m protein as a candidate vaccine established
the basis for the study of bivalent genetic engineering vaccines against PRRSV and PRV.
Translated from Journal of Biotechnology, 2005, 21(6): 858–864 [译自: 生物工程学报] 相似文献
11.
Xia Wu Qin-Mei Feng Ying Wang Jun Shi Hai-Liang Ge Wen Di 《Cancer immunology, immunotherapy : CII》2010,59(2):279-291
Till now, little is known about the effects of chemotherapy on the immunity of cancer patients and the ideal timing (“window”
period) for immunotherapy combined with chemotherapy. In this study, we addressed the immunogenicity of apoptotic ovarian
cancer cells induced by paclitaxel and carboplatin, the immunologic aspects in ovarian cancer patients under chemotherapy,
and the CTL response when CD8+ T cells were stimulated with tumor antigen in the “window” period. The immunogenicity of apoptotic ovarian cancer cells was
detected first. Then, blood samples from each ovarian cancer patient were obtained before (S0) and at days 5–7 (S1), days 12–14 (S2) and days 25–28 (S3) after chemotherapy. The proportions of immunocyte subsets and the function of NK cells were studied. We found that apoptotic
ovarian cancer cells elicited a powerful CTL response with antitumor activity in vitro. The proportions of CD3+ T cells, CD4+ T cells and the ratio of CD4+ to CD8+ cells did not change significantly on S1, S2 and S3, compared to S0, whereas the percentage of Treg cells decreased remarkably on S2. The proportions of Th1, Tc1, CD45RO memory T, NKT cells and the ratio of Tc1 to Tc2 cells increased significantly on S2. IFN-γ secreting CD8+ T cells also increased remarkably on S2, especially when CD8+ T cells were stimulated with autologous tumor antigen. From our point of view, chemotherapy induces temporary immune reconstitution
and augments anti-tumor immune response. It is probable that the “window” period of days 12–14 after chemotherapy provides
the best opportunity for immunotherapy. 相似文献
12.
Shenghua Zhou Anna M. Cerny Katherine A. Fitzgerald Evelyn A. Kurt-Jones Robert W. Finberg 《Journal of virology》2012,86(20):11254-11265
Type I interferons (IFNs), predominantly IFN-α and -β, play critical roles in both innate and adaptive immune responses against viral infections. Interferon regulatory factor 7 (IRF7), a key innate immune molecule in the type I IFN signaling pathway, is essential for the type I IFN response to many viruses, including lymphocytic choriomeningitis virus (LCMV). Here, we show that although IRF7 knockout (KO) mice failed to control the replication of LCMV in the early stages of infection, they were capable of clearing LCMV infection. Despite the lack of type I IFN production, IRF7 KO mice generated normal CD4+ T cell responses, and the expansion of naïve CD8+ T cells into primary CD8+ T cells specific for LCMV GP33–41 was relatively normal. In contrast, the expansion of the LCMV NP396-specific CD8+ T cells was severely impaired in IRF7 KO mice. We demonstrated that this defective CD8+ T cell response is due neither to an impaired antigen-presenting system nor to any intrinsic role of IRF7 in CD8+ T cells. The lack of a type I IFN response in IRF7 KO mice did not affect the formation of memory CD8+ T cells. Thus, the present study provides new insight into the impact of the innate immune system on viral pathogenesis and demonstrates the critical contribution of innate immunity in controlling virus replication in the early stages of infection, which may shape the quality of CD8+ T cell responses. 相似文献
13.
Wendy Ingram Shahram Kordasti Lucas Chan Linda D. Barber Gee J. Tye Nicola Hardwick Ghulam J. Mufti Farzin Farzaneh 《Cancer immunology, immunotherapy : CII》2009,58(10):1679-1690
Immunotherapeutic strategies are increasingly being explored as a method of enhancing anti-tumour immune responses in patients
with acute myeloid leukaemia (AML). Regulatory CD4+ T cells (Tregs) suppress effector T and natural killer (NK) cells and therefore pose a potential challenge to the efficacy
of immunotherapy. AML cells transduced with a lentivirus expressing CD80 (B7.1) and IL2 (LV-CD80/IL2) are capable of stimulating
T and NK cell cytotoxicity in vitro. This study examines the effect of CD80/IL2 modified AML cells on Treg number and function.
We report a significant increase in the number of CD8+ T cells (P = 0.046) CD3−CD56+ NK cells (P = 0.028) and CD3+CD4+CD25highFoxp3+ Tregs (P = 0.043) following stimulation for 7 days with allogeneic LV-CD80/IL2 AMLs. In contrast, autologous LV-CD80/IL2 AML cell
cultures provide a weaker stimulation with a lower number of CD8+ T cells (P = 0.011) and no change in NK cell or Treg numbers. However, an increase in cytotoxic CD8+ T cells and NK cells are detected following both allogeneic and autologous LV-CD80/IL2 stimulation as demonstrated by an
increase in IFN-γ and CD107a expression. Despite the presence of increased numbers of Tregs with suppressive activity in a
subset of cultures, increased lysis of unmodified AMLs was still achieved following allogeneic (day 0, 2.2%; day 7, 20.4%)
and more importantly, autologous LV-CD80/IL2 culture in which AML patients had recently received intensive chemotherapy (day
0, 0%; day 7, 16%). Vaccination with LV-CD80/IL2 therefore provides a potential strategy to enhance anti-leukaemia immune
responses without a concomitant stimulation of Treg-mediated inhibition of cytotoxic immunological responses. 相似文献
14.
H. Belfrage Mikael Dohlsten Gunnar Hedlund Terje Kalland 《Cancer immunology, immunotherapy : CII》1997,44(2):77-82
Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4+ and CD8+ T cells expressing certain families of T cell receptor (TCR) variable-region β (Vβ) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause
deletion and anergy of both CD4+ and CD8+ T cells, resulting in reduced frequency of SEA-responsive cells TCR-Vβ11+ as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive
CD4+ and CD8+ cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing down-regulation of endogenous
IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the
cytotoxic function of T cells, tumour necrosis factor α, interferon γ and IL-6, on a cellular level. These studies show that
continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T
cell activation and by prevention of the development of T cell deletion and anergy.
Received: 29 August 1996 / Accepted: 16 January 1997 相似文献
15.
Harrop R Ryan MG Myers KA Redchenko I Kingsman SM Carroll MW 《Cancer immunology, immunotherapy : CII》2006,55(9):1081-1090
5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26–h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8+ T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4+ T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4+ and CD8+ T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26–h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4+ T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model. 相似文献
16.
Zhang HG Chen HS Peng JR Shang XY Zhang J Xing Q Pang XW Qin LL Fei R Mei MH Leng XS Chen WF 《Cancer immunology, immunotherapy : CII》2007,56(12):1945-1954
The MAGE-A3 protein, one of the promising tumor antigens for immunotherapy, is highly expressed in human hepatocellular carcinoma
(HCC). In this study, we estimated the specific CD8+ T cell immune response to MAGE-A3 p271–279 peptide (M3271) in the peripheral blood of HCC patients without antigen vaccination in order to evaluate its immunotherapeutic potential
in these patients. After expansion in vitro, the functional IFN-γ producing M3271 specific CD8+ T cells were detected in 30.8% (8/26) of HLA-A2+MAGE-A3+ HCC patients. The effector CD8+ T cells could release cytotoxic molecules of granzyme B and perforin after restimulation with natural HLA-A2+MAGE-A3+ HCC cell lines in the samples tested. The functional supertype of HLA-A2 in the presentation of HLA-A*0201 restricted M3271 peptide has been identified in the Chinese HCC patients of Han ethnicity, that widely expanded the applicability of this
tumor peptide vaccine in Chinese HCC patients. Thus, the functionally detectable pre-existence of M3271-specific CD8+ T cells in HCC patients makes M3271 a potential target for immunotherapy in these patients. The responsive CD8+ T cells to both NY-ESO-1 and MAGE-A3 antigens provide a rationale for the application of a bivalent vaccine in HCC patients
with tumors expressing both antigens.
H-G Zhang, H-S Chen, and J-R Peng are contributed equally to this paper. 相似文献
17.
Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment 总被引:1,自引:0,他引:1
Bergmann C Strauss L Zeidler R Lang S Whiteside TL 《Cancer immunology, immunotherapy : CII》2007,56(9):1429-1442
Objective Chronic inflammation and cancer development are associated with dysregulated immune responses and the presence of regulatory
T cells (Treg). To study the role of Treg in tumor cell escape from immune surveillance, an in vitro model simulating the tumor microenvironment and promoting the
induction and expansion of IL-10+ Treg type 1 (Tr1) was established.
Methods An in vitro co-culture system (IVA) included an irradiated head and neck squamous cell carcinoma cell line, immature dendritic
cells (iDC), CD4+CD25− T cells and cytokines, IL-2 (10 IU/ml), IL-10 (20 IU/ml), IL-15 (20 IU/ml) ± 1 nM rapamycin. Autologous iDC and CD4+CD25− T cells were obtained from the peripheral blood of 15 normal donors. Co-cultures were expanded for 10 days. Proliferating
lymphocytes were phenotyped by multi-color flow cytometry. Their suppressor function was measured in CFSE inhibition assays ± neutralizing
anti-IL-10 mAb and using transwell cultures. Culture supernatants were tested for IL-4, IL-10, TGF-β and IFN-γ in ELISA.
Results In the IVA, low doses of IL-2, IL-10 and IL-15 promoted induction and expansion of CD3+CD4+CD25−IL2Rβ+IL2Rγ+FoxP3+CTLA-4+IL-10+ cells with suppressor activity (mean suppression ± SD = 58 ± 12%). These suppressor cells produced IL-10 (mean ± SD = 535 ± 12 pg/ml)
and TGF-β (mean ± SD = 512 ± 38 pg/ml), but no IL-4 or IFN-γ. Suppressor function of co-cultures correlated with the percent
of expanding IL-10+ Tr1 cells (r
2 = 0.9; P < 0.001). The addition of rapamycin enriched Tr1 cells in all co-cultures. Neutralizing anti-IL-10 mAb abolished suppressive
activity. Suppression was cell-contact independent.
Conclusion The tumor microenvironment promotes generation of Tr1 cells which have the phenotype distinct from that of CD4+CD25highFoxP3+ nTreg and mediate IL-10 dependent immune suppression in a cell-contact independent manner. Tr1 cells may play a critical
role in cancer progression. 相似文献
18.
Alves PM Faure O Graff-Dubois S Cornet S Bolonakis I Gross DA Miconnet I Chouaib S Fizazi K Soria JC Lemonnier FA Kosmatopoulos K 《Cancer immunology, immunotherapy : CII》2006,55(12):1515-1523
STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8+ T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP86–94 and STEAP262–270). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201+ STEAP+ human tumor cells. Furthermore, STEAP86–94 and STEAP262–270 stimulated specific CD8+ T cells from HLA-A*0201+ healthy donors, and these peptide specific CD8+ T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP86–94-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8+ T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy. 相似文献
19.
B. F. Banner L. Savas S. Baker B. A. Woda 《Virchows Archiv. B, Cell pathology including molecular pathology》1993,64(1):213-220
Little is known about the nature of the mucosa-associated immune system within the normal colon, or about the immune response
to colon carcinoma. In this study inflammatory cells (ICs) in 14 normal colons and 14 carcinomas were characterized. Overall
inflammation, lymphocytes, plasma cells, neutrophils, and eosinophils were graded in routine H & E sections. Frozen sections
were stained by an immunoperoxidase technique using antibodies to the T cell associated antigens CD2, CD7, CD4, CD8, and T
cell receptors αβ and γδ. B cells were identified with CD20, macrophages with CD68, and Class II antigen with anti-HLA DR.
Each cell type was semiquantitatively graded in 10 high power fields (HPFs) in the lumenal half (LH) or basal half (BH) of
the normal mucosae, and in epithelium or stroma of the carcinomas. In normal colons, ICs were more frequent in LH than in
BH. Plasma cells, lymphocytes and monocytes predominated. Subtyping of lymphocytes showed that CD4+ TCR αβ+ T lymphocytes were most numerous in the lamina propria. Lymphocytes within the epithelium were CD8+ T cells. Around carcinomas the overall grade of ICs was 1+ in the majority of cases. Plasma cells, CD4+ and CD8+ cells with the TCR αβ receptor, and macrophages were most frequent. Lymphoid aggregates of both T and B cells were frequent.
Conclusions: 1. Normal colon contains a diffuse lumenally oriented population of TCR αβ+ CD4+ T cells, plasma cells, macrophages and class II antigen-expressing cells in the lamina propria. Intraepithelial lymphocytes
are of the T suppressor phenotype. CD4+ T cells, macrophages and HLG-DR+ cells predominate in the response to colon carcinomas. 相似文献
20.
Lymphocyte subpopulations of regional lymph nodes in human colon and gastric adenocarcinomas 总被引:3,自引:0,他引:3
Beatriz Lores-Vazquez Margarita Pacheco-Carracedo Josefina Oliver-Morales Purificación Parada-Gonzalez F. Gambón-Deza 《Cancer immunology, immunotherapy : CII》1996,42(6):339-342
In order to study the host immune response to tumours, previous knowledge of the cellular composition of regional draining
lymph nodes is necessary. Enlarged regional lymph nodes are a common finding in colon and gastric adenocarcinomas. We have
studied the cellular composition of normal non-reactive and of regional draining lymph nodes of colon and gastric adenocarcinomas.
In normal non-reactive lymph nodes, T lymphocytes (CD2+, CD7+) constituted the largest fraction of the lymphoreticular cells. These lymphocytes were mainly CD4+, and there were more cells expressing the CD45RA isoform of the CD45 antigen than CD45RO. Reactive lymph nodes presented
a decreased proportion of CD4+ CD45RA+ cells and an increased number of B cells. Although most of the T cells in the reactive nodes were CD4+ CD45RO+, their proportion was similar to that found in normal non-reactive nodes. We studied the presence of the molecules CD28 and
CD80 involved in the processes of interaction and activation of T and B lymphocytes. The CD28 molecule was found in all the
T lymphocytes, while the CD80 molecule was weakly expressed on the B lymphocyte membrane.
Received: 4 January 1996 / Accepted: 28 May 1996 相似文献