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1.
To elicit a therapeutic antitumor immune response, dendritic cells (DCs) have been employed as a cellular adjuvant. Among various DC-based approaches, fusion of DCs and tumor cells potentially confers not only DC functionality, but also a continuous source of unaltered tumor antigens. We have recently demonstrated successful generation of fusion hybrids by a large-scale electrofusion technique. The immunogenicity and therapeutic potential of fusion hybrids were further analyzed in a model system of a murine melanoma cell line expressing beta-galactosidase (beta-gal) as a surrogate tumor antigen. A single vaccination with fusion hybrids plus IL-12 induced a therapeutic immune response against 3-day established pulmonary metastases. This immunotherapy was beta-gal specific and involved both CD4 and CD8 T cells. In vitro, fusion hybrids stimulated specific IFN-gamma secretion from both CD4 and CD8 immune T cells. They also nonspecifically induced IL-10 secretion from CD4 but not CD8 T cells. Compared to other DC loadings, our results demonstrate the superior immunogenicity of fusion. The current technique of electrofusion is adequately developed for clinical use in cancer immunotherapy. 相似文献
2.
Stoitzner P Green LK Jung JY Price KM Atarea H Kivell B Ronchese F 《Cancer immunology, immunotherapy : CII》2008,57(11):1665-1673
BACKGROUND: Transplantable B16 melanoma is widely used as a tumor model to investigate tumor immunity. We wished to characterize the leukocyte populations infiltrating B16 melanoma tumors, and the functional properties of tumor-infiltrating dendritic cells (TIDC). MATERIALS AND METHODS: We used the B16 melanoma cell line expressing ovalbumin protein (OVA) to investigate the phenotype and T cell stimulatory capacity of TIDC. RESULTS: The majority of leukocytes in B16 melanoma were macrophages, which colocalized with TIDCs, B and T cells to the peripheral area of the tumor. Both myeloid and plasmacytoid DC populations were present within tumors. Most of these DCs appeared immature, but about a third expressed a mature phenotype. TIDCs did not present tumor-derived antigen, as they were unable to induce the proliferation of tumor-specific CD4+ and CD8+ T cells in vitro unless in the presence of specific peptides. Some presentation of tumor-derived antigen could be demonstrated in the tumor-draining lymph node using in vivo proliferation assays. However, while proliferation of CD8+ T cells was reproducibly demonstrated, no proliferation of CD4+ T cells was observed. CONCLUSION: In summary, our data suggest that DCs in tumors have limited antigen-presenting function. Inefficient antigen presentation extends to the tumor-draining lymph node, and may affect the generation of antitumor immune responses. 相似文献
3.
Dendritic cells (DC), which consist of several different subsets, specialize in antigen presentation and are critical for mediating the innate and adaptive immune responses. DC subsets can be classified into conventional, plasmacytoid, and monocyte-derived DC in the tumor microenvironment, and each subset plays a different role. Because of the role of intratumoral DCs in initiating antitumor immune responses with tumor-derived antigen presentation to T cells, DCs have been targeted in the treatment of cancer. By regulating the functionality of DCs, several DC-based immunotherapies have been developed, including administration of tumor-derived antigens and DC vaccines. In addition, DCs participate in the mechanisms of classical cancer therapies, such as radiation therapy and chemotherapy. Thus, regulating DCs is also important in improving current cancer therapies. Here, we will discuss the role of each DC subset in antitumor immune responses, and the current status of DC-related cancer therapies. 相似文献
4.
Nabekura T Nagasawa T Nakauchi H Onodera M 《Cancer immunology, immunotherapy : CII》2008,57(5):611-622
Dendritic cells (DC), genetically modified to express ovalbumin by the retroviral vector GCDNsap, can elicit stronger anti-tumor
immunity than those loaded with the peptides. To assess the clinical feasibility of the strategy, such DC were prepared by
differentiation of hematopoietic progenitor cells transduced with the human epidermal growth factor receptor 2 (HER2). When
inoculated in mice, the DC primed both HER2-specific cytotoxic T lymphocytes and type 1 T helper lymphocytes, resulting in
production of HER2-specific antibody. Of importance is that the antibody mediated antibody-dependent cellular cytotoxicity
and opsonization. The potent anti-tumor effects were also confirmed by results of experiments using HER2-transgenic mice.
Inoculation of HER2-transduced DC resulted in longer disease-free survival of treated mice that showed significant reduction
of primary and metastatic tumors. Interestingly, footpad inoculation resulted in stronger anti-tumor effects compared to subcutaneous
administration and induced higher levels of the HER2-specific antibody, suggesting that an important role of humoral immunity
in anti-tumor effects for malignancies with membrane-type tumor-associated antigens (TAA). Taken together, vaccination of
the TAA-transduced DC may represent a promising form of therapy for breast cancers expressing HER2. 相似文献
5.
Le Poole IC ElMasri WM Denman CJ Kroll TM Bommiasamy H Lyons Eiben G Kast WM 《Cancer immunology, immunotherapy : CII》2008,57(6):789-797
Dendritic cells (DC) can be cytotoxic towards tumor cells by means of TNF family molecules expressed on the cell surface of
activated DCs. Tumor cells expressing appropriate receptors are killed by DC, generating a source of antigen to be presented
to the immune system. It has not been investigated whether Langerhans cells (LC) are selectively cytotoxic to tumor cells.
This is of particular interest for epithelial tumor cells that physically interact with LC in vivo. Among epithelial tumors,
the oncogenic process of cervical tumors is relatively well defined by their Human Papillomavirus (HPV) mediated etiology.
To study whether HPV16 E6 and E7 expressions, otherwise observed in cervical tumor cells, can sensitize normal cervical epithelial
cells to DC and LC mediated killing, the E6 and E7 genes were introduced by retroviral transfection, and cells were subsequently
used as targets in cytotoxicity assays. Expression of cytotoxic molecules by effector cells was measured in response to the
pro-inflammatory cytokine IFN-γ; cytotoxicity was established and concomitant expression of receptor molecules was assessed
on target cells. A correlation between the shrinkage of HPV16 E6 and E7+ tumors versus DC and LC infiltration was evaluated
in a murine model of cervical cancer. DC and LC proved to be equally cytotoxic towards E6 and E7 expressing cervical epithelial
cells. IFN-γ induced TRAIL expression by DC and LC, and inhibition of TRAIL partially blocked cytotoxic effects. Expression
of TRAIL decoy receptors was reduced following introduction of E6 and E7 into host cells. Shrinkage of HPV16 E6 and E7 expressing
tumors correlated with infiltration by S100+ DC and LC, co-localizing with apoptotic mouse tumor cells. In conclusion, DC
and LC mediated killing may be exploitable for anti-tumor treatment.
I. Caroline Le Poole and W.M. ElMasri have contributed equally to this paper. 相似文献
6.
Teramoto K Kontani K Fujita T Ozaki Y Sawai S Tezuka N Fujino S Itoh Y Taguchi O Kannagi R Ogasawara K 《Cancer immunology, immunotherapy : CII》2007,56(3):331-342
We reported previously that pigeon cytochrome c-derived peptides (Pan-IA), which bind broad ranges of MHC class II molecules efficiently, activate T helper (Th) function in mice. In an experimental model, Pan-IA DNA vaccines augmented antitumor immunity in tumor antigen-immunized mice. To elicit more potent antitumor immunity and to eradicate tumors in a therapeutic setting, Pan-IA-loaded dendritic cells (DCs) were inoculated in combination with vaccines including ovalbumin (OVA) antigen DNA in tumor-bearing mice. Seventy percent of the immunized mice survived tumor-free for at least 4 months after treatment. In contrast, mice vaccinated with OVA DNA, either with or without naïve DCs, did not eliminate the tumors and died within 5 weeks. Only in mice vaccinated with OVA DNA and Pan-IA-loaded DCs were both cytotoxic and helper responses specific for OVA induced at the spleen and tumor sites as well as at the vaccination sites. Furthermore, accumulation of OVA-specific CD4+ and CD8+ T lymphocytes and interferon-gamma-mediated anti-angiogenesis were observed in the tumors of these mice. Thus, the combined vaccination primed both tumor-specific cytotoxicity and helper immunity resulting in augmented tumor lysis ability and anti-angiogenic effects. This is the first report to show that most established tumors were successfully eradicated by collaboration of potent antitumor immunity and anti-angiogenic effects by vaccination with tumor antigens and helper-activating analogs. This novel vaccination strategy is broadly applicable, regardless of identifying helper epitopes in target molecules, and contributes to the development of therapeutic cancer vaccines. 相似文献
7.
There has been a recent interest in using IL-15 to enhance antitumor activity in several models because of its ability to
stimulate CD8+ T cell expansion, inhibit apoptosis and promote memory T cell survival and maintenance. Previously, we reported that C6VL
tumor lysate-pulsed dendritic cell vaccines significantly enhanced the survival of tumor-bearing mice by stimulating a potent
tumor-specific CD8+ T cell response. In this study, we determined whether IL-15 used as immunologic adjuvant would augment vaccine-primed CD8+ T cell immunity against C6VL and further improve the survival of tumor-bearing mice. We report that IL-15 given after C6VL
lysate-pulsed dendritic cell vaccines stimulated local and systemic expansion of NK, NKT and CD8+ CD44hi T cells. IL-15 did not, however, augment innate or cellular responses against the tumor. T cells from mice infused with IL-15
following vaccination did not secrete increased levels of tumor-specific TNF-α or IFN-γ or have enhanced C6VL-specific CTL
activity compared to T cells from recipients of the vaccine alone. Lastly, IL-15 did not enhance the survival of tumor-bearing
vaccinated mice. Thus, while activated- and memory-phenotype CD8+ T cells were dramatically expanded by IL-15 infusion, vaccine-primed CD8+ T cell specific for C6VL were not significantly expanded. This is the first account of using IL-15 as an adjuvant in a therapeutic
model of active immunotherapy where there was not a preexisting pool of tumor-specific CD8+ T cells. Our results contrast the recent studies where IL-15 was successfully used to augment tumor-reactivity of adoptively
transferred transgenic CD8+ T cells. This suggests that the adjuvant potential of IL-15 may be greatest in settings where it can augment the number and
activity of preexisting tumor-specific CD8+ T cells. 相似文献
8.
Homing of intravenously and intralymphatically injected human dendritic cells generated in vitro from CD34+ hematopoietic progenitor cells 总被引:6,自引:0,他引:6
Andreas Mackensen Thomas Krause Uli Blum Peter Uhrmeister Roland Mertelsmann Albrecht Lindemann 《Cancer immunology, immunotherapy : CII》1999,48(2-3):118-122
Dendritic cells (DC) are professional antigen-presenting cells that can be generated in vitro from CD34+ peripheral blood progenitor cells by recombinant cytokines. These cells have potential implications for immunotherapeutic
approaches in the treatment of cancer and other diseases. Physiologically, immature DC in the periphery capture and process
antigens, then mature to interdigitating DC and migrate to lymphoid organs, where they activate lymphocytes. However, it is
not known if DC generated in vitro have the capacity to traffic in vivo to the lymphoid tissues, such as spleen and lymph
nodes. We have investigated whether human radiolabeled DC differentiated in vitro migrate and localize to lymphoid tissues
after intravenous and intralymphatic injection. The distribution and localization of the DC were evaluated in five patients
with malignant melanoma using serial whole-body gamma camera imaging. Intravenously infused DC demonstrated transient lung
uptake followed by localization in the spleen and liver for at least 7 days. DC injected into a lymphatic vessel at the dorsal
foot were rapidly detected in the draining lymph nodes where they remained for more than 24 h. These data suggest that DC
differentiated in vitro localize preferentially to lymphoid tissue, where they could induce specific immune responses.
Received: 28 January 1999 / Accepted: 4 March 1999 相似文献
9.
We have developed immuno-gene therapy for malignant melanoma and prostate cancer. The therapy is based on monocyte-derived dendritic cells (DCs) that are transfected with autologous melanoma-mRNA or mRNA from three prostate cancer cell lines (DU-145, LN-CaP and PC-3). A broad spectrum of tumour-associated antigens will be included in both DC-vaccines. The use of autologous melanoma-mRNA moreover allows targeting of individual tumour antigens that are specific to each patient. Effective protocols have been established for mRNA-transfection by square wave electroporation and for the generation of clinical grade DCs. A full scale preclinical evaluation demonstrated in vitro T cell responses in 6/6 advanced melanoma patients. The responses were specific to antigens encoded by the transfected tumour-mRNA. Recently, we have conducted two phase I/II trials, in advanced malignant melanoma and androgen-resistant prostate cancer. Successful vaccine preparations were obtained for all 41 patients elected. No serious adverse effects were observed. Specific T cell responses (T cell proliferation and/or IFNγ ELISPOT) were demonstrated in 9/19 evaluable melanoma patients and in 12/19 prostate cancer patients. The response rates were higher for patients receiving intradermal vaccination, compared to intranodal injection. Thirteen prostate cancer patients developed a decrease in log-slope PSA. The PSA-response was significantly related to the T cell response (P=0.002). We conclude that the DC-vaccine is feasible and safe, and that T cell responses are elicited in about 50% of patients.This article is a symposium paper from the Annual Meeting of the “International Society for Cell and Gene Therapy of Cancer”, held in Shenzhen, China, on 9–11 December 2005. 相似文献
10.
肠相关淋巴组织在防御病毒、细菌、寄生虫等有害物质入侵中发挥着重要作用,是消化道屏障的组成部分,其中肠道树突状细胞尤为重要,作为目前所知的机体内功能最强的专职性抗原呈递细胞,在肠道内,树突状细胞不但能对病原菌产生免疫应答,还能对肠腔内的正常菌群和各种食物蛋白产生免疫耐受,因此了解树突状细胞的功能及相关作用机制有着重要意义.现就对树突状细胞的生物学特性,以及其在肠道免疫中的作用进行综述. 相似文献
11.
Wurzenberger C Koelzer VH Schreiber S Anz D Vollmar AM Schnurr M Endres S Bourquin C 《Cancer immunology, immunotherapy : CII》2009,58(6):901-913
Dendritic cell (DC) vaccines have emerged as a promising strategy to induce antitumoral cytotoxic T cells for the immunotherapy
of cancer. The maturation state of DC is of critical importance for the success of vaccination, but the most effective mode
of maturation is still a matter of debate. Whereas immature DC carry the risk of inducing tolerance, extensive stimulation
of DC may lead to DC unresponsiveness and exhaustion. In this study, we investigated how short-term versus long-term DC activation
with a Toll-like receptor 9 agonist influences DC phenotype and function. Murine DC were generated in the presence of the
hematopoietic factor Flt3L (FL-DC) to obtain both myeloid and plasmacytoid DC subsets. Short activation of FL-DC for as little
as 4 h induced fully functional DC that rapidly secreted IL-12p70 and IFN-α, expressed high levels of costimulatory and MHC
molecules and efficiently presented antigen to CD4 and CD8 T cells. Furthermore, short-term activated FL-DC overcame immune
suppression by regulatory T cells and acquired high migratory potential toward the chemokine CCL21 necessary for DC recruitment
to lymph nodes. In addition, vaccination with short-term activated DC induced a strong cytotoxic T-cell response in vivo and
led to the eradication of tumors. Thus, short-term activation of DC generates fully functional DC for tumor immunotherapy.
These results may guide the design of new protocols for DC generation in order to develop more efficient DC-based tumor vaccines. 相似文献
12.
13.
Vujanovic L Whiteside TL Potter DM Chu J Ferrone S Butterfield LH 《Cancer immunology, immunotherapy : CII》2009,58(1):121-133
Recombinant adenoviral vectors (AdV) are potent vehicles for antigen engineering of dendritic cells (DC). DC engineered with
AdV to express full length tumor antigens are capable stimulators of antigen-specific polyclonal CD8+ and CD4+ T cells. To
determine the impact of AdV on the HLA class I antigen presentation pathway, we investigated the effects of AdV transduction
on antigen processing machinery (APM) components in human DC. Interactions among AdV transduction, maturation, APM regulation
and T cell activation were investigated. The phenotype and cytokine profile of DC transduced with AdV was intermediate, between
immature (iDC) and matured DC (mDC). Statistically significant increases in expression were observed for peptide transporters
TAP-1 and TAP-2, and HLA class I peptide-loading chaperone ERp57, as well as co-stimulatory surface molecule CD86 due to AdV
transduction. AdV transduction enhanced the expression of APM components and surface markers on mDC, and these changes were
further modulated by the timing of DC maturation. Engineering of matured DC to express a tumor-associated antigen stimulated
a broader repertoire of CD8+ T cells, capable of recognizing immunodominant and subdominant epitopes. These data identify
molecular changes in AdV-transduced DC (AdV/DC) that could influence T cell priming and should be considered in design of
cancer vaccines. 相似文献
14.
Dendritic cells presenting tumor antigen 总被引:13,自引:0,他引:13
Michael R. Shurin 《Cancer immunology, immunotherapy : CII》1996,43(3):158-164
Since the first identification of dendritic cells by Steinman and Cohn in 1973, progress in understanding their biology has
included the development of novel methods of cell culture, recognition of critical aspects of migration and maturation, and
appreciation of their major role as antigen-presenting cells (APC), and how this activity is regulated by cytokines and expression
of accessory molecules. Dendritic cells are the major APC involved in the initiation of the immune response and the development
of tolerance. There is considerable evidence that they can acquire antigen in the peripheral tissues and process, transport,
and present it to T cells in secondary lymphoid tissue. A number of studies show that, in vitro or in vivo, antigen-pulsed
dendritic cells can directly sensitize T cells and stimulate the development of antigen-specific immune responses, including
both protective and therapeutic antitumor responses. In this paper, several important aspects of dendritic cell biology are
discussed and a number of studies confirming the role of these professional APC in antitumor immunity are reviewed.
Received: 6 August 1996 / Accepted: 20 September 1996 相似文献
15.
Immunization with heat shock protein 105-pulsed dendritic cells leads to tumor rejection in mice 总被引:3,自引:0,他引:3
Yokomine K Nakatsura T Minohara M Kira J Kubo T Sasaki Y Nishimura Y 《Biochemical and biophysical research communications》2006,343(1):269-278
Recently, we reported that heat shock protein 105 (HSP105) DNA vaccination induced anti-tumor immunity. In this study, we set up a preclinical study to investigate the usefulness of dendritic cells (DCs) pulsed with mouse HSP105 as a whole protein for cancer immunotherapy in vivo. The recombinant HSP105 did not induce DC maturation, and the mice vaccinated with HSP105-pulsed BM-DCs were markedly prevented from the growth of subcutaneous tumors, accompanied with a massive infiltration of both CD4+ T cells and CD8+ T cells into the tumors. In depletion experiments, we proved that both CD4+ T cells and CD8+ T cells play a crucial role in anti-tumor immunity. Both CD4+ T cells and CD8+ T cells specific to HSP105 were induced by stimulation with HSP105-pulsed DCs. As a result, vaccination of mice with BM-DCs pulsed with HSP105 itself could elicit a stronger tumor rejection in comparison to DNA vaccination. 相似文献
16.
Uptake and presentation of malignant glioma tumor cell lysates by monocyte-derived dendritic cells 总被引:4,自引:0,他引:4
De Vleeschouwer S Arredouani M Adé M Cadot P Vermassen E Ceuppens JL Van Gool SW 《Cancer immunology, immunotherapy : CII》2005,54(4):372-382
Malignant glioma of the CNS is a tumor with a very bad prognosis. Development of adjuvant immunotherapy is hampered by interindividual and intratumoral antigenic heterogeneity of gliomas. To evaluate feasibility of tumor vaccination with (autologous) tumor cells, we have studied uptake of tumor cell lysates by dendritic cells (DCs), and the T-cell stimulatory capacity of the loaded DCs. DCs are professional antigen-presenting cells, which have already been used as natural adjuvants to initiate immune responses in human cancer. An efficacious uptake of tumor cell proteins, followed by processing and presentation of tumor-associated antigens by the DCs, is indeed one of the prerequisites for a potent and specific stimulation of T lymphocytes. Human monocytes were differentiated in vitro to immature DCs, and these were loaded with FITC-labeled tumor cell proteins. Uptake of the tumor cell proteins and presentation of antigens in the context of both MHC class I and II could be demonstrated using FACS analysis and confocal microscopy. After further maturation, the loaded DCs had the capacity to induce specific T-cell cytotoxic activity against tumor cells. We conclude that DCs loaded with crude tumor lysate are efficacious antigen-presenting cells able to initiate a T-cell response against malignant glioma tumor cells. 相似文献
17.
树突状细胞受曲霉菌抗原冲击后的变化 总被引:2,自引:0,他引:2
目的探讨树突状细胞(DCs)在曲霉菌免疫中的作用以及曲霉菌抗原冲击对DCs功能的影响。方法小鼠骨髓制备DCs,于小鼠尾静脉接种,以3H-TdR掺入法检测DCs刺激小鼠脾脏T细胞分化能力,ELISA方法检测IFN-γ和IL-12的浓度,电镜观察DCs的形态,同时进行DCs的表型测定。结果电镜下可见DCs细胞形态不规则,表面伸展出大量树突,与曲霉菌共同培养后胞内含有大量的烟曲霉孢子,部分孢子的膜被破坏;与烟曲霉孢子共培养24h后,DCs细胞表形CD40、CD80、CD86的表达明显增高,产生IL-12p70约(700.40±93.75)pg/ml,明显高于对照组(141.96±52.06)pg/ml;烟曲霉抗原冲击DCs回输小鼠的脾脏T细胞增殖能力明显增强,体外接受烟曲霉抗原24h产生IFN-γ(1084.33±238.04)pg/ml,明显高于单纯DCs接种小鼠的脾脏T细胞(345.98±32.75)pg/ml(p<0.01)。结论DCs能吞噬并破坏加热灭活的烟曲霉孢子,并趋于成熟,抗原呈递能力增加。 相似文献
18.
Terry J. Fry Jessica L. Shand Matthew Milliron Sarah K. Tasian Crystal L. Mackall 《Cancer immunology, immunotherapy : CII》2009,58(8):1257-1264
Dendritic cells (DCs) serve as central regulators of adaptive immunity by presenting antigens and providing necessary co-signals.
Environmental information received by the DCs determines the co-signals delivered to the responding adaptive cells and, ultimately,
the outcome of the interaction. DCs loaded with relevant antigens have been used as therapeutic cellular vaccines, but the
optimal antigen loading method has not been determined. We compared different methods to load class I and class II epitopes
from the male antigenic complex, HY, onto DCs for the potency of the immune response induced in vivo. Co-incubation of female
DCs with HY peptides, RNA or cell lysate from HY expressing tumor induced immune responses equivalent to male DCs. In contrast,
female DCs incubated with irradiated, apoptotic HY expressing tumor cells (or male B cells) generated a stronger immune response
than male DCs or female DCs loaded using any of the other methods. DC loading with apoptotic tumor resulted in complete protection
against high dose HY-expressing tumor challenge whereas 100% lethality was observed in groups receiving DCs that were loaded
with peptides, RNA, or lysate. We conclude that signals provided to the DCs by apoptotic cells substantially augment the potency
of DC vaccines. 相似文献
19.
Yin Ji Piao So-Hyun Yoon Hoe Suk Kim Woo Kyung Moon Wonshik Han 《Biochemistry and Biophysics Reports》2021
We here evaluated the therapeutic effect of tumor cell-derived exosomes (TEXs)-stimulated dendritic cells (DCs) in a syngeneic orthotopic breast tumor model. The DC line DC2.4 and breast cancer cell line E0771 originally isolated from C57BL/6 mice were used. E0771 cells stably expressing the exosomal CD63-RFP or luciferase (Luc) and DC2.4 cells stably expressing GFP were produced using lentivirus. TEXs were purified from conditioned medium of E0771/CD63-RFP cells. Breast tumor model was established by injecting E0771/Luc cells into mammary gland fat pad of mice. TEXs contained immune modulatory molecules such as HSP70, HSP90, MHC I, MHC II, TGF-β, and PD-L1. TEXs were easily taken by DC2.4 cells, resulting in a significant increase in the in vitro proliferation and migration abilities of DC2.4 cells, accompanied by the upregulation of CD40. TEX-DC-treated group exhibited a decreased tumor growth compared with control group. CD8+ cells were more abundant in the tumors and lymph nodes of TEX-DC-treated group than in those of control group, whereas many CD4+ or FOXP3+ cells were localized in those of control group. Our results suggest a potential application of TEX-DC-based cancer immunotherapy. 相似文献
20.
树突状细胞是最强的抗原提呈细胞,在免疫系统中发挥着着重要作用。Toll样受体是表达在树突状细胞上的一种PRRs,主要功能是通过识别病原体微生物所携带的病原相关分子模式激活DC,使其分泌各种免疫调节细胞因子,从而启动免疫应答。在肠道免疫中TLR信号的激活为肠道提供保护作用。本文简述了树突状细胞的生物特性、不同亚型。重点阐述了Toll样受体在肠道免疫中的作用及益生菌对肠道Toll样受体表达的影响。 相似文献