Natural killer cells 56bnght16- have higher counts in the umbilical cord blood than in the adult peripheral blood

ABSTRACT Introduction and hypothesis: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for allogeneic hematopoietic stem cell transplantation in the absence of a compatible donor. The UCB transplantation has a lower incidence of chronic graft versus host disease (GvHD), but is associated with slower engraftment and slower immune reconstitution, compared to other sources. Dendritic cells (DCs) and Natural Killer cells (NKs) play a central role in the development of GvHD and the graft versus leukemia (GvL) effect, as well as in the control of infectious complications. Method: We quantified by multiparametric flow cytometry monocytes, lymphocytes, NK cells, and DCs, including their subsets, in UCB samples from 54 healthy newborns and peripheral blood (PB) from 25 healthy adult volunteers. Results: In the UCB samples, there were higher counts of NK cells 56bright16- (median 0.024 × 109/L), compared to the PB samples (0.012 × 109/L, p < 0.0001), NK 56dim16bright (median 0.446 × 109/L vs. 0.259 × 109/L for PB samples, p = 0.001) and plasmacytoid dendritic cells (pDCs, median 0.008 × 109/L for UCB samples vs. 0.006 × 109/L for PB samples, p = 0.03). Moreover, non-classic monocyte counts were lower in UCB than in PB (median 0.024 × 109/L vs. 0.051 × 109/L, respectively, p < 0.0001). Conclusion: In conclusion, there were higher counts of NK cells and pDCs and lower counts of non-classic monocytes in UCB than in PB from healthy individuals. These findings might explain the lower incidence and severity of chronic GvHD, although maintaining the GvL effect, in UCB transplant recipients, compared to other stem cell sources.

Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Immunology of a unique biological structure: the Echinococcus laminated layer

The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (Insp6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL "debris" at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium Insp6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.

Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively.@*RESULTS@#4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine.@*CONCLUSION@#The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.

Study on the mechanism of VEGF inducing tolerogenic dendritic cells in oral squamous cell carcinoma / 口腔医学

Objective@#To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC).@*Methods@#The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. @*Results@#Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group.@*Conclusion@#VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Research progress on therapeutic DC vaccine against melanoma / 药学实践杂志

Melanoma is the most aggressive skin malignant tumor, which is prone to early metastasis and relapse after treatment. Therapeutic tumor vaccines are new immunotherapies, which have the advantages of low toxicity and inhibiting tumor metastasis. Melanoma has a high mutation load and a large number of specific antigens. Currently, various types of tumor vaccines have been developed for melanoma, especially those based on dendritic cells (DC). Although the efficacy of therapeutic DC vaccines in melanoma has been confirmed by a number of studies, these vaccines still have problems such as insufficient immune effect and poor efficacy when used alone, and there is still a large room for improvement. In this paper, the current research status of therapeutic DC vaccines for melanoma was reviewed, and the research key points and optimization strategy of therapeutic DC tumor were prospected.

Immunoprotective role of dendritic cells in Chlamydia muridarum respiratory infection / 中华微生物学和免疫学杂志

Objective:To investigate the role of dendritic cells (DC) in Chlamydia muridarum ( Cm) respiratory infection and their effect on adaptive immune response. Methods:C57BL/6 mice were exposed to 1×10 3 inclusion-forming units (IFU) of Cm through inhalation to establish the mouse model of Cm respiratory infection. The proportion of CD11c + MHCⅡ + DC and the expression of costimulatory molecules (CD40, CD80 and CD86) in spleen tissues were detected by flow cytometry on 0, 3 and 7 d after infection. The expression of IL-12p40, IL-10 and IL-6 at mRNA level in spleen tissues was detected by qPCR. Mouse splenic DC isolated on 7 d after Cm infection were sorted by magnetic beads and then transferred to recipient mice. Th1 response in the recipient mice was measured using intracellular cytokine staining 14 d after infection. Results:Cm respiratory infection induced massive infiltration of DC and promoted the expression of costimulatory molecules on splenic DC. The expression of IL-12 and IL-10 at mRNA level in splenic DC reached the peak on 3 d after infection. Transferring the splenic DC of Cm-infected mice into the recipient mice could alleviate the disease condition in the recipient mice after Cm infection with reduced Cm inclusion-forming units in lung tissues and significantly increased proportion of Th1 cells in lung and spleen tissues. Conclusions:Cm respiratory infection could induce the maturation and activation of DC, which promoted Th1 immune response. DC played an important role in Cm infection.

CT features of inflammatory pseudotumor like follicular dendritic cell sarcoma of the spleen / 中华肝胆外科杂志

Objective:To explore the CT features of inflammatory pseudotumor like follicular dendritic cell sarcoma (FDCS) of the spleen.Methods:The clinical data of 12 patients with splenic inflammatory pseudotumor like FDCS admitted to 3 central hospitals including Yongjia People's Hospital in Zhejiang Province from January 2015 to December 2022 were retrospectively analyzed, including 4 males and 8 females, with a median age of 60 years old. The number, shape, size and CT features of the lesions were analyzed based on patient's CT image data.Results:CT scans of 12 patients showed 15 lesions, including 10 single lesions and 2 multiple lesions. The lesions were circular in 5 cases, elliptical in 4 cases, and irregular in 3 cases. The median maximum diameter of the mass is 6.5 cm. On plain scan, all 12 tumors showed low density or slightly low density. The CT value is (41.3±7.2) HU; 8 cases had uneven density and 4 cases had uniform density. There were 8 cases with clear tumor boundaries and 4 cases with unclear boundaries. There were 8 cases with tumor necrosis and cystic transformation, and 5 cases showed patchy bleeding lesions in the center of the tumor. Enhancement: the arterial phase shows small patches or flocculent enhancement at the edges or parenchymal parts of the tumor, with CT value of (56.0±3.8) HU. Among them, there were 7 cases of mild enhancement, 4 cases of moderate enhancement, and 1 case of significant enhancement. During the portal phase, there was mild to moderate persistent small patchy uneven enhancement, with CT value of (62.0±4.3) HU. Among them, there were 8 cases of mild enhancement and 4 cases of moderate enhancement. The delayed phase showed a slow withdrawal of enhancement, with CT value of (45.0±8.2) HU. All 12 cases underwent complete resection and were diagnosed with FDCS through pathological examination.Conclusion:FDCS plain scan shows circular or elliptical uneven low-density masses, with small patches or flocculent light to moderate uneven enhancement in the arterial phase, continuous enhancement in the portal phase, and slow withdrawal in the delayed phase as the main characteristics.

Chemotherapy Combined with Venetoclax Followed by Allo-Hematopoietic Stem Cell Transplantation for Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of chemotherapy combined with venetoclax followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#The clinical data of 3 patients with BPDCN undergoing allo-HSCT in Department of Hematology, Wuhan First Hospital from July 2017 to November 2021 were collected and retrospectively analyzed.@*RESULTS@#Among the 3 patients, there were 1 male and 2 females, aged 27-52 years old. Skin lesions were observed during initial diagnosis, and it could also be characterized by acute leukemia. Characteristic molecular markers of tumor cells, such as CD4, CD56, CD123, and CD303 were positive. In addition, the expression detection of Bcl-2 in 3 patients were positive. Chemotherapy combined with venetoclax in the initial induction of chemotherapy (1 case) or disease recurrence and progress (2 cases) was performed. There were 2 cases evaluated as complete remission (CR) and 1 case as partial remission (PR) before allo-HSCT. The patients all received a nonmyeloablative conditioning without total body irradiation (TBI). The prevention programme of graft-versus-host disease (GVHD) was antithymocyte globulin + mycophenolate mofetil + cyclosporin A/FK506 ± methotrexate. The number of mononuclear cell (MNC) count was (16.73-18.35)×108/kg, and CD34+ cell count was (3.57-4.65)×106/kg. The 3 patients were evaluated as CR after allo-HSCT (+21 to +28 d), the donor-recipient chimerism rate was 100%, and Ⅲ-Ⅳ GVHD was not observed. One patient died at +50 d after transplantation, two patients were followed up for 28 months and 15 months, respectively, and achieved disease-free survival (DFS).@*CONCLUSIONS@#BPDCN is a highly aggressive malignant tumor with poor prognosis. Chemotherapy combined with venetoclax followed by allo-HSCT may lead to long-term DFS or even cure. Post-transplant maintenance is still unclear.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Blastic plasmacytoid dendritic cell neoplasm: A clinico-pathological retrospective analysis of thirteen cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinicopathological features of blastic plasmacytoid dendritic cell neoplasm (BPDCN).@*METHODS@#A total of 13 cases of BPDCN diagnosed in Peking University First Hospital from January 2013 to March 2022 were collected. The clinical features, histopathological characteristics, immunophenotypes and prognosis of the patients were analyzed retrospectively, and the related literatures was reviewed as well.@*RESULTS@#Among the 13 patients, 11 were male and 2 were female, with a median age of 62 years (ranging from 5 to 78 years). Among them, single organ involvement occurred in 5 cases, all of which presented with skin lesions. Two or more organs were involved in other 8 cases (single organ with bone marrow involved in 3 cases; skin, bone marrow and lymph node involved simultaneously in 3 cases; skin, bone marrow, lymph node and spleen involved simultaneously in 2 cases). Histopathologically, it was characterized by the proliferation of medium to large atypical blastic cells, which infiltrated the whole thickness of dermis. When involved, the bone marrow lesions mainly appeared in a diffuse pattern, while the lymph node structure was usually destroyed, and the red pulp of the affected spleen was diffusely invaded. Immunohistochemical staining showed that all the 13 cases were positive for CD4, CD56, and CD123 (13/13) in varying degrees. All the 9 cases expressed TCL1 (9/9). Variable expression of CD68 (KP1) (8/13), TdT (7/12), CD117 (2/6), and high Ki-67 proliferation index (40%~80%) were showed. The neoplastic cells lacked expressions of CD20, CD3, MPO, CD34, or CD30; EBER in situ hybridization were negative (0/9). After definite diagnosis, 6 cases received chemotherapy, among which 1 received adjuvant radiotherapy, and 2 received subsequent bone marrow transplantation. Another 2 cases only received maintenance treatment. The median follow-up time was 14 months (ranging from 6 to 36 months), 5 patients died of the disease (6 to 18 months), 3 patients survived (7 to 36 months up to now), and the remaining 5 patients lost follow-up.@*CONCLUSION@#BPDCN is a rare type of malignant lymphohematopoietic tumor with aggressive behavior and poor prognosis. The diagnosis should be made combining clinical features, histopathology, and immunohistochemical phenotype. Attention should be paid to differentiating BPDCN from other neoplasms with blastoid morphology or CD4+CD56+ tumors.

Histopathological and immunohistochemical clues to the illusive diagnosis of follicular dendritic cell sarcoma: A clinicopathological masquerader

Follicular dendritic cell sarcoma is a rare histiocytic and dendritic neoplasm mainly involving the lymph nodes and selective extranodal sites. They are often misdiagnosed due to nonspecific clinical, radiological, and morphological findings in addition to their rarity. Four cases described below had variable age of presentation, site of involvement, size of the lesion, and histopathological features. Application of an extensive immunohistochemical panel, including a combination of >1 dendritic cell marker, clinched the diagnosis. A combination of D2-40 and Cluster of differentiation 21 (CD21) worked best in establishing a definite role in the current series. Programmed death-ligand 1 (PD-L1) analysis was positive in two of the three cases where it could be performed. However, none of our cases had received immunotherapy. Prompt recognition of the described histopathology features and incorporation of novel immunohistochemical markers can translate to timely initiation of therapy for this aggressive disease

Comparison of primary follicular lymphoma of gastrointestinal tract and secondary involvement: A study from South India

Primary follicular lymphoma of the gut (PFL-GI) is a rare entity. This study aims to compare the clinicopathologic features of PFL-GI with cases of gastrointestinal involvement by disseminated nodal follicular lymphoma. This is a retrospective study with 6 cases of primary follicular lymphoma and 8 cases of secondary involvement of the gut, over a period of 9 years. The slides and blocks were retrieved and reviewed. Clinical data was obtained from hospital records. Clinicopathologic features were compared. PFL-GI cases had a slightly higher median age group (p value 0.23) and no gender predilection when compared to cases with secondary involvement which showed a female preponderance. Para-aortic lymphadenopathy was seen in all secondary cases whereas none of the primary cases showed significant lymphadenopathy. The only microscopic feature that was different was the presence of hollowed out pattern of immunostaining for follicular dendritic cells seen in all cases of PFL-GI but in none of the secondary cases

Progress in microRNA/lncRNA regulating dendritic cell differentiation, maturation and function / 中华微生物学和免疫学杂志

Dendritic cells (DC) as professional antigen-presenting cells can activate na?ve T cells and play an important role in bridging innate immunity and acquired immunity. Therefore, the differentiation and maturation of DC and the mechanism in its function regulatory have attracted much attention. With the rapid development of high-throughput sequencing, noncoding RNAs (ncRNAs) have been gradually known. In recent years, increasing studies have reported that ncRNAs play an importantly role in regulating the differentiation and maturation of DC. In this paper, the regulatory effects of microRNAs and long ncRNAs on the differentiation, maturation and function of DC were reviewed.

Recent advances on the role of various cells-derived exosomes in ocular surface / 中华实验眼科杂志

Exosomes are membranous vesicles secreted by cells and can be widely involved in intercellular communication, anti-inflammation, immunoregulation, etc.Mesenchymal stem cell (MSC), regulatory T cell (Treg), immature dendritic cell (imDC) and myeloid-derived suppressor cell (MDSC) are the main ocular surface-related exosomes origins.Exosomes derived from different cells play their roles by delivering different biological molecules to recipient cells.Exosomes derived from MSC play a positive role in ocular surface inflammation and immune-related diseases by inhibiting T cell proliferation, transforming macrophage phenotype, regulating T helper (Th) cell differentiation and up-regulating Treg expression, reduce neovascularization and inflammation, and foster a microenvironment to promote corneal wound healing at the same time.Exosomes derived from Treg contain inducible NO synthase and microRNA (miRNA) including miR-503, miR-330 and miR-9, which can interfere with cell cycle progression, induce apoptosis, induce the differentiation of other T cells into Treg phenotype, inhibit T cell allograft rejection to induce immune tolerance.Exosomes derived from imDC inhibit corneal allograft rejection by delivering miR-682.MDSC-derived exosomes promote Treg expansion in vivo and in vitro, inhibit the proliferation and cytotoxicity of activated T cells, and express miR-29a-3p and miR-93-5p, which can inhibit the differentiation of Th1 and Th17 cells.Given the anti-inflammatory and immunosuppressive effects of exosomes, this paper reviewed the studies on ocular surface inflammation and immune-related diseases such as corneal injury, mucopolysaccharide storage disease, dry eye, Sj?gren syndrome and ocular graft-versus-host disease.

Changes and significance of lymphocyte subsets in recipients with acute rejection after liver transplantation / 器官移植

Objective To evaluate the changes and significance of lymphocyte subsets in the recipients with acute rejection after liver transplantation. Methods The recipients presenting with acute rejection after liver transplantation were assigned into the rejection group (n=17), and their counterparts with stable liver function were allocated into the control group (n=17) according to the ratio of 1∶1 by propensity score matching method. The incidence of acute rejection after liver transplantation was analyzed, and the concentration of tacrolimus in the recipients was compared between two groups. The absolute value and proportion of lymphocyte subsets in peripheral blood were compared between two groups. The diagnostic value of lymphocyte subsets for acute rejection after liver transplantation was assessed by the receiver operating characteristic (ROC) curve. The absolute value and proportion of lymphocyte subsets in the rejection group were compared before and after treatment. Results Among 17 recipients in the rejection group, 4 cases developed acute rejection within postoperative 28 d, and 13 cases had acute rejection within postoperative 29-180 d. No significant difference was noted in the tacrolimus concentration between two groups (P=0.295). Compared with the control group, the proportions of peripheral blood T cells, CD4+T cells, B cells and natural killer (NK) T cells were significantly increased in the rejection group (all P < 0.05). The elevated proportion of NKT cells in the early stage after liver transplantation was an independent risk factor for acute rejection following liver transplantation[odds ratio (OR) 1.774, 95% confidence interval (CI) 1.059-2.971, P=0.029]. ROC curve analysis showed that the area under curve (AUC) of CD4+T cells, B cells and NKT cells was 0.76, 0.73 and 0.77, respectively. The AUC of combined use of CD4+T cells, B cells and NKT cells was 0.89, with a cut-off value of 0.69, sensitivity of 0.706 and specificity of 0.941. After corresponding treatment, all recipients were gradually recovered, and liver functions were eventually restored to normal in the rejection group. After treatment, the proportion of T cells, CD4+T cells, CD8+T cells and NK cells was significantly decreased (all P < 0.05). Conclusions The elevated proportion of NKT cells indicates an increased risk of acute rejection after liver transplantation. Combined use of CD4+T cells, B cells and NKT cells may deliver early detection and diagnosis of acute rejection after liver transplantation.

Ureaplasma urealyticum GrpE promotes mouse dendritic cell maturation and elicits Th1 immune responses / 中华微生物学和免疫学杂志

Objective:To investigate the effects of Ureaplasma urealyticum GrpE ( Uu-GrpE) on the maturation of dendritic cells and the polarization of T cells. Methods:Uu-GrpE was expressed and purified, and then identified by Western blot. The cytotoxicity of Uu-GrpE to mouse bone marrow-derived dendritic cells (BMDCs) was analyzed by LDH kit. After stimulating BMDCs with Uu-GrpE, the expression of costimulatory molecules, CD80, CD86 and major histocompatibility complex Ⅱ (MHCⅡ), on the surface of BMDCs was detected by flow cytometry, and ELISA was used to detect the cytokines such as IL-12p70, TNF-α, IL-1β and IL-6. CD4 + Na?ve T cells were isolated from mouse spleen tissues by magnetic beads. A co-culture system of BMDCs and Na?ve T cells was constructed to analyze the effects of GrpE-stimulated mature BMDCs (GrpE-BMDCs) on T cell proliferation and polarization towards Th1/Th2. Mice were immunized with GrpE-BMDCs through the tail vein, and the induced humoral and cellular immune responses were detected by ELISA and flow cytometry. Results:Uu-GrpE was successfully express and high purity BMDCs were isolated. Uu-GrpE could stimulate BMDCs to secrete cytokines such as IL-12p70, TNF-α, IL-1β and IL-6 without having cytotoxicity. Uu-GrpE significantly increased the expression of CD80 [mean flourscence indensity (MFI): (324.00±22.11) vs (91.03±10.95), P<0.01], CD86 [MFI: (1 176.00±51.39) vs (217.00±14.93), P<0.01] and MHCⅡ [MFI: (708.70±56.32) vs (185.70±16.77), P<0.01] on BMDCs. Compared to the GrpE-BMDCs only group and GrpE (boiled)-BMDCs+ T cell group, the GrpE-BMDCs+ T cell group showed significantly increased T cell proliferation [stimulation index: (7.25±0.21) vs(6.55±0.23) and (6.09±0.35), both P<0.05], and dramatically promoted T cell secretion of IL-2 and IFN-γ [IL-2: (145.60±14.67) pg/ml vs(55.92±3.12) pg/ml and (26.05±2.40) pg/ml, P<0.05 and P<0.01; IFN-γ: (267.20±37.80) pg/ml vs(146.70±20.65) pg/ml and(27.84±6.69) pg/ml, both P<0.05]. However, no significant change was observed in the expression of Th2-type cytokines. Moreover, the adoptive transfer of GrpE-BMDCs induced a Th1-type immune response. Conclusions:Uu-GrpE could stimulate the maturation and polarization of BMDCs. Moreover, it could induce Th1 immune response as a candidate protein vaccine for Ureaplasma urealyticum.