Intestinal antigen-presenting cells in mucosal immune homeostasis:Crosstalk between dendritic cells,macrophages and B-cells

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.

Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells

AIM:To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.METHODS:Cinnamon extract was used to treat murine macrophage cell line(Raw 264.7),mouse primary antigen-presenting cells(APCs,MHCII+) and CD11c+dendritic cells to analyze the effects of cinnamon extract on APC function.The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production,and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry.In addition,the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis,respectively.To confirm the anti-inflammatory effects of cinnamon extract in vivo,cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid.The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms,histological analysis and cytokine expression prof iles in inflamed tissue.RESULTS:Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells(DCs) by suppressing expression of co-stimulatory molecules(B7.1,B7.2,ICOS-L),MHCII and cyclooxygenase(COX)-2.Cinnamon extract induced regulatory DCs(rDCs) that produce low levels of pro-inflammatory cytokines [interleukin(IL)-1β,IL-6,IL-12,interferon(IFN)-γ and tumor necrosis factor(TNF)-α] while expressing high levels of immunoregulatory cytokines(IL-10 and transforming growth factor-β).In addition,rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation,and converted CD4+ T cells into IL-10high CD4+ T cells.Furthermore,oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines(IL-1β,IFN-γ and TNF-α),while enhancing IL-10 levels.CONCLUSION:Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.

Impact of PRRSV on activation and viability of antigen presenting cells

Porcine reproductive and respiratory syndrome(PRRS) is one of the most important diseases of swine industry. The causal agent, PRRS-virus(PRRSV), is able to evade the host immune response and survive in the organism causing transient infections. Despite all scientific efforts, there are still some gaps in the knowledge of the pathogenesis of this disease. Antigen presenting cells(APCs), as initiators of the immune response, are located in the first line of defense against microorganisms, and are responsible for antigen recognition, processing and presentation. Dendritic cells(DCs) are the main type of APC involved in antigen presentation and they are susceptible to PRRSV infection. Thus, PRRSV replication in DCs may trigger off different mechanisms to impair the onset of a host effective immune response against the virus. On the one side, PRRSV may impair the basic functions of DCs by regulating the expression of major histocompatibility complex class Ⅱ and CD80/86. Other strategy followed by the virus is the induction of cell death of APCs by apoptosis, necrosis or both of them. The impairment and/or cell death ofAPCs could lead to a failure in the onset of an efficient immune response, as long as cells could not properly activate T cells. Future aspects to take into account are also discussed in this review.

Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus

Systemic lupus erythematosus （SLE） is a typical autoimmune disease involving multiple systems and organs. Ample evidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This study was undertaken to investigate the mechanisms of interaction between antigen presenting cells （APCs） and an autoreactive T cell （ATLI） clone obtained from lupus-prone BXSB mice. ATLI cells, either before or after 7-ray irradiation, were able to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able to stimulate the proliferation of resting ATL 1 cells at a responder/stimulator （R/S） ratio of 1/2.5. Dendritic cells （DCs） were much more powerful stimulators for ATLI cells on a per cell basis. The T cell stimulating ability ofmacrophages and B cells, but not DCs, was sensitive to T-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were able to block DC-mediated stimulation of ATL 1 proliferation, indicating cognate recognition between ATL 1 and APCs. Our data suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotal role in keeping the momentum of autoimmune responses leading to autoimmune diseases.

Changes of the Transcriptional Levels of Molecules Associated with Endogenous Antigen Processing and Presentation in Porcine Skin-derived Dendritic Cells Infected with PCV2 in vivo

[Objective] This study aimed to investigate the changes of the transcriptional levels of molecules associated with endogenous antigen processing and presenta- tion in porcine skin-derived dendritic cells infected with PCV2 in vivo. [Method] Healthy 40-day-old Landrace piglets were infected with porcine circovirus type 2 （PCV2） and euthanized on the 34, 7rd, 14th, 21st and 35th d post inoculation （DPI）. The porcine skin-derived dendritic cells （DCs） were collected to analyze the transcrip- tional levels of molecules （LMP7, UBP, MHC-I, calreticulin） associated with endogenous antigen processing and presentation by using real-time fluorescent quantitative PCR （real-time FQ-PCR）. [Result] The results showed that the level of LMP7 mR- NAs was reduced significantly on the 3DPI （P〈0.05）; the level of UBP mRNAs was consistently up-regulated, which increased significantly on the 21DPI and 35DPI （P〈 0.05）; the level of MHC-I mRNAs was significantly down-regulated on the 7DPI （P〈 0.05）; the level of calreticulin mRNAs was up-regulated slightly without significant dif- ference. [Conclusion] PCV2 can inhibit the endogenous antigen processing and presentation ability of porcine skin-derived DCs at early stages of infection.

Impact of nanoparticles on immune cells and their potential applications in cancer immunotherapy

Nanoparticles represent a heterogeneous collection of materials,whether natural or synthetic,with dimensions aligning in the nanoscale.Because of their intense manifestation with the immune system,they can be harvested for numerous bio-medical and biotechnological advancements mainly in cancer treatment.This review article aims to scrutinize various types of nanoparticles that interact differently with immune cells like macrophages,dendritic cells,T lymphocytes,and natural killer(NK)cells.It also underscores the importance of knowing how nanoparticles influence immune cell functions,such as the production of cytokines and the presentation of antigens which are crucial for effective cancer immunotherapy.Hence overviews of bio-molecular mechanisms are provided.Nanoparticles can improve antigen presentation,boost T-cell responses,and overcome the immunosuppressive tumor environment.The regulatory mechanisms,signaling pathways,and nanoparticle characteristics are also presented for a comprehensive understanding.We review the nanotechnology platform options and challenges in nanoparticlesbased immunotherapy,from an immunotherapy perspective including precise targeting,immune modulation,and potential toxicity,as well as personalized approaches based on individual patient and tumor characteristics.The development of emerging multifunctional nanoparticles and theranostic nanoparticles will provide new solutions for the precision and efficiency of cancer therapies in next-generation practice.

Cilostazol inhibits plasmacytoid dendritic cell activation and antigen presentation

Background Cilostazol, an anti-platelet drug for treating coronary heart disease, has been reported to modulate immune cell functions Plasmacytoid dendritic cells （pDCs） have been found to participate in the progression of atherosclerosis mainly through interferon ct （IFN-ct） production. Whether cilostazol influences pDCs activation is still not clear. In this study, we aimed to investigate the effects of cilostazol on cell activation and antigen presentation ofpDCs in vitro in this study. Methods Peripheral blood mononuclear cells isolated by Ficoll cen- trifugation and pDCs sorted by flow cytometry were used in this study. After pretreated with cilostazol for 2 h, cells were stimulated with CpG-A, R848 or virus for 6 h or 20 h, or stimulated with CpG-B for 48 h and then co-cultured with naive T cell for five days. Cytokines in supernatant and intracellular cytokines were analyzed by ELISA or flow cytometry respectively. Results Our data indicated that cilostazol could inhibit IFN-α and tumor necrosis factor α （TNF-α） production from pDCs in a dose-dependent manner. In addition, the ability of priming na ve T cells of pDCs was also impaired by cilostazol. The inhibitory effect was not due to cell killing since the viability of pDCs did not change upon cilostazol treatment. Conclusion Cilostazol inhibits pDCs cell activation and antigen presentation in vitro, which may explain how cilostazol protects against atherosclerosis.

Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical success.During ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor response.While effective,this process is resource-intensive and logistically impossible for many patients.Particulate artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo ACT.While particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after injection.Barriers to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of interest.Biomaterial properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell stimulation.Previous literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in vitro.With the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive transfer.Using this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

HBsAg loading on dendritic cells in patients with chronic hepatitis B: expressions of phenotypic molecules

BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B(CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed. METHODS: Forty patients with CHB were divided randomly into 4 groups(10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GMCSF) and interleukin 4(IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5mg/L, 5mg/L and 10mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry. RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope. The expression of phenotypic molecules on DCs in the control group was as low as CD83 (8.02±3.99)%, CD80(8.77±2.06)%, and MHC-DR (14.05±2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83(18.35±2.93)%, CD80(42.63±7.15)% and MHC-DR(47.49±6.59)% in 2.5mg/L HBsAg loading group, CD83(17.88±3.12)%, CD80(45.24± 10.93)% and MHC-DR(47.07±8.52)% in 5mg/L HBsAg loading group and CD83(16.74±2.86)%, CD80(44.59±6.99)% and MHC-DR(48.59±7.42)% in 10mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05). CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.

Inducible expression of endomorphins in murine dendritic cells

Bone marrow precursor cells were extracted from C57BL/6J mice aged 7-8 weeks, and dendritic cells were purified using anti-CD1 lc （a specific marker for dendritic cells） antibody-coated magnetic beads. Immunofluorescence staining revealed that the expression levels of endomorphin-1 and endomorphin-2 were upregulated in dendritic cells activated by lipopolysaccharide. An enzyme Jmmunoassay showed that lipopolysaccharide and other Toll-like receptor ligands promoted the secretion of endomorphin-1 and endomorphin-2 from activated dendritic cells. [3H]-thymidine incorporation demonstrated that endomorphin-1 and endomorphin-2 both inhibited the proliferation of T lymphocyte induced by activated dendritic cells. Furthermore, this immunosuppressive effect was blocked by CTOP, a specific antagonist of IJ-opioid receptors. Our experimental findings indicate that activated dendritic cells can induce the expression and secretion of endomorphins, and that endomorphins suppress T lymphocyte proliferation through activation of iJ-opioid receptors.

Role of Dendritic Cells in Myocarditis Induced by Coxsackie B_3 Virus in Mouse

Background and Objectives Autoimmune reaction may play an important role in the pathogenesis and progress in virus myocarditis. Dendritic cells are the initiators of immune reaction to foreign antigens and are considered to be key players in the induction and maintenance of autoimmune reactions. This study was undertaken to investigate the role of DC in mice with virus myocarditis. Methods and Results Fifty Balb/c mice were injected Coxsackie B3 virus to induce myocarditis and ten mice were injected culture liquid as control group. The hearts of virus - infected mice were harvested on day 3, 7, 14, 28 after the injection. All the hearts were sliced to do HE staining, MHC Ⅱ antigen and S - 100 protein immunohistochemical staining. The inflammation response and expression of MHC Ⅱ antigen and S - 100 protein positive stained cells were observed. The MHC Ⅱ antigen positive score were 1.42±0.95, 2.24 ±1. 00, 3. 23± 1. 16, 2. 58 ± 1. 05 respectively in group 3d, 7 d, 14 d, 28 d, which were significant different from control group(0. 50 ±0.75, P <0. 05). The S-100 positive staining cells in control group was 3. 2±1. 0. And the numbers were 6. 7 ± 1. 4 , 16. 4 ± 2. 5 , 21. 2±3. 3 , 13. 4 ± 2. 3 respectively in group 3 d, 7 d, 14 d, 28 d, and there were significant differences compared with the control group ( P < 0. 01) . Conclusions Immune reaction was involved in the pathogenesis in Coxsackie B3 virus - induced myocarditis in mouse, and dendritic cell might play an important role in the immune reaction.

Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

Following organ transplantation, the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14 - 30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2αR and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significantly positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR was clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.

Antigen-presenting effects of effector memory Vγ9Vδ2 T cells in rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells （the predominant subtype of γδ T cells in peripheral blood） were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4＋ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon （IFN）-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4＋ T cells, thus sustaining CD4＋ T-cell activation.

Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8^+ T Cells Ex Vivo

Artificial antigen-presenting cells are expected to stimulate the expansion and acquisition of optimal therapeutic features of T cells before infusion. Here CD32 that binds to a crystallizable fragment of IgG monoclonal antibody was genetically expressed on human K562 leukemia cells to provide a ligand for T-cell receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28 and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These artificial modified cells had the abilities of inducing CD8^＋ T cell activation, promoting CD8^＋ T cell proliferation, division, and long-term growth, inhibiting CD8^＋ T cell apoptosis, and enhancing CD8^＋ T cell secretion of IFN-T and perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28 days. This approach was robust, simple, reproducible and economical for expansion and activation of CD8^＋ T cells and may have important therapeutic implications for adoptive immunotherapy. Cellular ＆ Molecular Immunology.

T细胞免疫反应载体疫苗在人类疾病预防和治疗中的应用

人类疾病,特别是传染病和癌症,对公共卫生安全和全球经济构成前所未有的挑战。预防和治疗性疫苗的开发是应对人类疾病的优先对策。本文综述了疫苗载体的免疫学原理、T细胞载体疫苗设计策略及疫苗研究进展,为新型疫苗的设计提供新的思路。T细胞可以在机体发生感染后分化成不同的效应T细胞群,它们可以起到清除病原体的作用,关于效应T细胞功能和机制的研究对于设计能够引发基于T细胞免疫的疫苗至关重要。目前很多病毒(例如HIV、HCMV感染)和肿瘤疫苗的研发都侧重于T细胞类疫苗,在所有疫苗种类中,激活T细胞免疫反应的载体疫苗具有显著优势。许多来源的载体,包括病毒载体、细菌载体和核酸载体,它们在抗原提呈能力、免疫原性和保护效力方面都有良好的表现。此外,还总结了T细胞载体疫苗设计的策略,包括确定适当的抗原提呈途径和载体递送途径、确保生物安全性、如何选择合适的疫苗的载体、各种载体疫苗的优缺点等,尤其是mRNA疫苗在应对新冠疫情中发挥了重要的作用。疫苗载体的技术进步将会加速新型疫苗的研发,并且能促进人们对突发公共卫生事件的应对。

单细胞测序揭示心脏移植物中树突状细胞和B细胞的抗原提呈特性

目的探讨心脏移植物中树突状细胞(DC)和B细胞的抗原提呈特性。方法将BALB/c小鼠的心脏移植到C57BL/6J小鼠腹腔内,术后5 d(急性排斥反应早期)提取并流式分选心脏移植物中的CD45+细胞,进行单细胞RNA测序。以心脏移植物中的DC和B细胞的亚群为主要对象,通过生物信息学分析和流式细胞术,研究其在心脏移植后变化趋势、抗原提呈能力及其与T细胞之间的胞间通讯情况。采用基因本体(GO)功能富集差异分析佐证细胞亚群特异性功能和细胞亚群注释可信度。结果生发中心样B细胞(GC-L B)是急性排斥反应期心脏移植物中增幅最大、比例高达87%的B细胞亚群,经典DC(cDC)2是心脏移植急性排斥期间唯一大量增多的DC亚群,占44%,是心脏移植后与T细胞的胞间通讯中占据最高通讯强度的DC亚群;单核样DC(moDC)与记忆性B细胞(MBC)是未心脏移植中T细胞输入信号的主要发出者,而在心脏移植后急性排斥反应期中,转变为cDC2与GC-L B;其中MBC与GC-L B分别是心脏移植前后的主要T细胞输入信号来源。结论在未移植心脏和移植心脏指向T细胞的胞间通讯中,与DC相比,B细胞均占据更高的通讯数量和权重,推测在心脏移植急性排斥反应早期,B细胞的抗原提呈活动比DC更加活跃,强度更大。

APC在结核杆菌低分子多肽抗原体外激活人外周血γ^(δ+)T细胞中的作用

目的探讨抗原递呈细胞APC在结核杆菌Mtb低分子多肽抗原体外激活人外周血γδ+T细胞中的作用。方法用平皿粘附和尼龙毛柱纯化法,从PBMC中分离单核细胞、B淋巴细胞然后分别与纯化的T细胞共育在Mtb抗原的刺激下,观察γδ+T细胞的增殖效应。结果Mtb低分子多肽抗原在激活γδ+T细胞时,需要单核细胞、B细胞等APC的存在但APC并不起摄取、加工、递呈抗原的作用。结论γδ+T细胞具有与γδ+T细胞不同的独特抗原识别方式。

B细胞在非感染性葡萄膜炎中的研究进展

非感染性葡萄膜炎是一种严重威胁视力,治疗棘手的自身免疫性眼病。目前主流观点认为非感染性葡萄膜炎的发病机制是主要由CD4+T细胞介导的免疫失衡。但近年来许多证据表明B细胞也发挥关键作用,通过产生抗体、抗原提呈、分泌细胞因子、形成异位淋巴结构等多种方式参与到实验性自身免疫性葡萄膜炎模型及人类葡萄膜炎中。针对B细胞的治疗已广泛应用于多种自身免疫性疾病。利妥昔单抗,一种B细胞抑制剂,在对传统皮质类固醇和免疫抑制剂治疗无效的难治性非感染性葡萄膜炎中发挥不错疗效。本文总结了B细胞在非感染性葡萄膜炎中的作用及细胞疗法,旨在为更深入的机制研究提供理论基础,并为开发精准有效的防治策略开辟新视角。

抗原提呈细胞亚群预测肝癌患者的免疫治疗疗效研究

背景原发性肝细胞癌(hepatocellular carcinoma,HCC)患者中免疫治疗应用广泛,但需寻找有效的疗效预测标志物,以此提供个体化和精准化的治疗。目的探讨抗原提呈细胞(antigen presenting cell,APC)亚群与HCC患者免疫治疗的疗效关系。方法前瞻性纳入2022年5月—2023年9月在解放军总医院第五医学中心初次接受免疫治疗的中晚期HCC患者,通过流式细胞仪检测免疫治疗前的B细胞/淋巴细胞(B/LYM)、巨噬细胞/所有核细胞(MA/TNC)和树突细胞/所有核细胞(DC/TNC)的比值。根据均值将患者分为高水平组和低水平组,并比较两组间无进展生存期(progression free survival,PFS),并通过Cox分析影响PFS的因素。最后利用ROC曲线预测疾病控制的效能。结果共纳入84例患者,中位年龄为57岁;男性58例,女性26例。APC亚群基线数据:B/LYM均值为16.54%±6.27%,MA/TNC均值为9.14%±2.87%,DC/TNC均值为0.051%±0.021%。Kaplan-Meier生存分析和Cox回归分析显示B/LYM高值组的mPFS显著高于低值组(5.90个月vs 5.50个月,P=0.019;HR=0.588,95%CI:0.358~0.966),MA/TNC低值组的mPFS显著高于高值组(7.20个月vs 5.40个月,P=0.034;HR=0.617,95%CI:0.374~1.019),DC/TNC高值组的mPFS显著高于低值组(6.30个月vs 5.50个月,P=0.026;HR=0.615,95%CI:0.378~0.955)。且高水平的MA/TNC是疾病进展的独立危险因素,高水平的DC/TNC、B/LYM是疾病进展的保护因素。基线B/LYM、MA/TNC、DC/TNC对HCC患者接受2周期治疗后的疾病控制情况而言,具有较好的预测效能,且联合应用时效能进一步提高,AUC分别为0.685、0.723、0.745、0.865。结论高DC/TNC、B/LYM水平和低MA/TNC水平的HCC患者,可能更容易从免疫治疗中获益。

真菌毒素对树突状细胞免疫应答的影响

真菌毒素是病原真菌产生的次级代谢产物,常污染多种农作物,通过食物链对人畜健康造成严重危害。真菌毒素具有多种毒性作用,包括神经毒性、肝毒性、免疫毒性、致畸性和致癌性等,但其免疫毒性机制尚不完全清楚。树突状细胞(DCs)作为功能最强大的抗原提呈细胞,在启动先天免疫和获得性免疫应答中发挥重要作用。现有研究发现真菌毒素能够影响DCs的内吞作用、刺激T细胞活化的能力以及细胞因子和趋化因子的分泌,本文旨在综述真菌毒素对DCs免疫应答的影响,为后续研究阐明真菌毒素的免疫毒性机制提供参考。