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1.
Background
Invariant natural killer T (iNKT) cells develop in the thymus and branch off from the maturation pathway of conventional T cell at the DP stage. While different stages of iNKT cellular development have been defined, the actual time that iNKT cell precursors spend at each stage is still unknown.Methodology/Principal Finding
Here we report on maturation dynamics of post-selection DN iNKT cells by injecting wild-type DPdim thymocytes into the thymus of TCRα−/− mice and using the Vα14-Jα18 rearrangements as a molecular marker to follow the maturation dynamics of these cells.Conclusion/Significance
This study shows that the developmental dynamics of DN iNKT cells in DPdim are very rapid and that it takes less than 1 day to down-regulate CD4 and CD8 and become DN. These DN cells are precursors of peripheral DN iNKT cells and appear in the spleen in 1–2 days. Thymic DN iNKT residents are predominantly derived from cells that quickly return from the periphery. The expansion of a very small subset of DN iNKT precursors could also play a small role in this process. These data are an example of measuring T cell maturation in the thymus and show that the maturation dynamics of selected DN iNKT cells fall within the same general time frame as conventional αβ T cells. 相似文献2.
Chung SH Seki K Choi BI Kimura KB Ito A Fujikado N Saijo S Iwakura Y 《Arthritis research & therapy》2010,12(5):R188
Introduction
Chemokines and their receptors are potential therapeutic targets in rheumatoid arthritis (RA). Among these, several studies suggested the involvement of CXC chemokine 4 (CXCR4) and its ligand CXC ligand 12 (SDF-1) in RA pathogenesis. However, the role of these molecules in T-cell function is not known completely because of embryonic lethality of Cxcr4- and Cxcl12- deficient mice. In this report, we generated T cell-specific Cxcr4 -deficient mice and showed that the CXCR4 in T cells is important for the development of collagen-induced arthritis (CIA). 相似文献3.
Matteo Bellone Monica Ceccon Matteo Grioni Elena Jachetti Arianna Calcinotto Anna Napolitano Massimo Freschi Giulia Casorati Paolo Dellabona 《PloS one》2010,5(1)
Background
CD1d-restricted invariant NKT (iNKT) cells are a subset of T lymphocytes endowed with innate effector functions that aid in the establishment of adaptive T and B cell immune responses. iNKT cells have been shown to play a spontaneous protective role against experimental tumors. Yet, the interplay between iNKT and tumor-specific T cells in cancer immune surveillance/editing has never been addressed. The transgenic adenocarcinoma of the mouse prostate (TRAMP) is a realistic model of spontaneous oncogenesis, in which the tumor-specific cytotoxic T cell (CTL) response undergoes full tolerance upon disease progression.Principal Findings
We report here that lack of iNKT cells in TRAMP mice resulted in the appearance of more precocious and aggressive tumors that significantly reduced animal survival. TRAMP mice bearing or lacking iNKT cells responded similarly to a tumor-specific vaccination and developed tolerance to a tumor-associated antigen at comparable rate.Conclusions
Hence, our data argue for a critical role of iNKT cells in the immune surveillance of carcinoma that is independent of tumor-specific CTL. 相似文献4.
Ponpan Matangkasombut Wilawan Chan-in Anunya Opasawaschai Pisut Pongchaikul Nattaya Tangthawornchaikul Sirijitt Vasanawathana Wannee Limpitikul Prida Malasit Thaneeya Duangchinda Gavin Screaton Juthathip Mongkolsapaya 《PLoS neglected tropical diseases》2014,8(6)
Background
Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection.Methods
Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured.Results
iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated.Conclusion
iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future. 相似文献5.
Sophie Servais Catherine Menten-Dedoyart Yves Beguin Laurence Seidel André Gothot Coline Daulne Evelyne Willems Lo?c Delens Stéphanie Humblet-Baron Muriel Hannon Frédéric Baron 《PloS one》2015,10(6)
Background
Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented.Methods
In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation.Results
Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naïve CD4+, central memory CD4+ and naïve CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease.Conclusions
Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses. 相似文献6.
Camilla Tincati Matteo Basilissi Elisabetta Sinigaglia Esther Merlini Giovanni Carpani Antonella d’Arminio Monforte Giulia Marchetti 《PloS one》2014,9(10)
Background
Invariant Natural Killer T (iNKT) cells represent a determinant in the course of infections and diseases, however, their role in the pathogenesis of non-infectious co-morbidities in HIV-positive patients is unknown.Methods
Flow cytometry was used to investigate iNKT cell frequency, phenotype and function in HIV-infected patients on HAART with bone and/or cardiovascular disorders and in HIV-positive controls free from co-morbidities.Results
iNKT cells from subjects with bone and cardiovascular impairment expressed high levels of CD161 and predominantly secreted TNF. iNKT cells from individuals with bone disease alone did not show any distinctive phenotypical or functional characteristics. The functional capacity of iNKT cells in patients with cardiovascular disorder was impaired with no cytokine release upon stimulation.Conclusion
iNKT cells may have a role in non-infectious co-morbidities in treated HIV disease, possibly through the exacerbation of inflammation. Further studies are needed to investigate iNKT cells in the pathogenesis of non-communicable disorders in HIV infection. 相似文献7.
Taojun He Fang Zhang Jin Zhang Shanshan Wei Jie Ning Hanmei Yuan Bin Li 《Helicobacter》2023,28(3):e12959
Background and aims
Although Helicobacter pylori is recognized as an extracellular infection bacterium, it can lead to an increase in the number of CD8+ T cells after infection. At present, the characteristics of H. pylori antigen-specific CD8+ T cells and the epitope response have not been elucidated. This study was focused on putative protective antigen UreB to detect specific CD8+ T-cell responses in vitro and screen for predominant response epitopes.Methods
The PBMCs collected from H. pylori-infected individuals were stimulated by UreB peptide pools in vitro to identify the immunodominant CD8+ T-cell epitopes. Furthermore, their HLA restriction characteristics were detected accordingly by NGS. Finally, the relationship between immunodominant responses and appearance of gastric symptoms after H. pylori infection was conducted.Results
UreB-specific CD8+ T-cell responses were detected in H. pylori-infected individuals. Three of UreB dominant epitopes (A-2 (UreB443–451: GVKPNMIIK), B-4 (UreB420–428: SEYVGSVEV), and C-1 (UreB5–13: SRKEYVSMY)) were firstly identified and mainly presented by HLA-A*1101, HLA-B*4001 and HLA-C*0702 alleles, respectively. C-1 responses were mostly occurred in H. pylori-infected subjects without gastric symptoms and may alleviate the degree of gastric inflammation.Conclusions
The UreB dominant epitope-specific CD8+ T-cell response was closely related to the gastric symptoms after H. pylori infection, and the C-1 (UreB5-13) dominant peptides may be protective epitopes. 相似文献8.
Masanobu Horikoshi Daisuke Goto Seiji Segawa Yohei Yoshiga Keiichi Iwanami Asuka Inoue Yuki Tanaka Isao Matsumoto Takayuki Sumida 《PloS one》2012,7(12)
Objective
Invariant natural killer T (iNKT) cells regulate collagen-induced arthritis (CIA) when activated by their potent glycolipid ligand, alpha-galactosylceramide (α-GalCer). Glucose-6-phosphate isomerase (GPI)-induced arthritis is a closer model of human rheumatoid arthritis based on its association with CD4+ T cells and cytokines such as TNF-α and IL-6 than CIA. Dominant T cell epitope peptide of GPI (GPI325-339) can induce arthritis similar to GPI-induced arthritis. In this study, we investigated the roles of activation of iNKT cells by α-GalCer in GPI peptide-induced arthritis.Methods
Arthritis was induced in susceptible DBA1 mice with GPI peptide and its severity was assessed clinically. The arthritic mice were treated with either the vehicle (DMSO) or α-GalCer. iNKT cells were detected in draining lymph nodes (dLNs) by flow cytometry, while serum anti-GPI antibody levels were measured by enzyme-linked immunosorbent assay. To evaluate GPI peptide-specific cytokine production from CD4+ T cells, immunized mice were euthanized and dLN CD4+ cells were re-stimulated by GPI-peptide in the presence of antigen-presenting cells.Results
α-GalCer induced iNKT cell expansion in dLNs and significantly decreased the severity of GPI peptide-induced arthritis. In α-GalCer-treated mice, anti-GPI antibody production (total IgG, IgG1, IgG2b) and IL-17, IFN-γ, IL-2, and TNF-α produced by GPI peptide-specific T cells were significantly suppressed at day 10. Moreover, GPI-reactive T cells from mice immunized with GPI and α-GalCer did not generate any cytokines even when these cells were co-cultured with APC from mice immunized with GPI alone. In vitro depletion of iNKT cells did not alter the suppressive effect of α-GalCer on CD4+ T cells.Conclusion
α-GalCer significantly suppressed GPI peptide-induced arthritis through the suppression of GPI-specific CD4+ T cells. 相似文献9.
Hanxiang Nie Qiaoyu Yang Guqin Zhang Ailing Wang Qing He Min Liu Ping Li Jiong Yang Yi Huang Xuhong Ding Hongying Yu Suping Hu 《PloS one》2015,10(4)
Background
Invariant natural killer T cells (iNKT cells) are a unique subset of T lymphocytes and are considered to play an important role in the development of allergic bronchial asthma. Recently, iNKT cells were shown to play an immunoregulatory role in CD4+ and CD8+ T cell-mediated adaptive immune response. Allergen-specific Th2 inflammatory responses are an important part of the adaptive immune response in asthma. However, the regulatory functions of the Th2 inflammatory response in asthma have not been studied in detail.Method
In this study, we have investigated the regulatory functions of iNKT cells on the Th2 inflammatory response in an ovalbumin (OVA)-induced murine model of asthma.Results
Our results demonstrate that α-Galactosylceramide (α-GalCer) administration activated iNKT cells but could not induce the Th2 inflammatory response in wild-type (WT) mice. In the OVA-induced asthma model, α-GalCer administration and adoptive transfer of iNKT cells significantly augmented the Th2 inflammatory responses, including elevated inflammatory cell infiltration in the lung and bronchoalveolar lavage fluid (BALF); increased levels of IL-4, IL-5, and IL-13 in the BALF and splenocyte culture supernatant; and increased serum levels of OVA-specific IgE and IgG1. In addition, the Th2 inflammatory response was reduced, but not completely abrogated in CD1d-/- mice immunized and challenged with OVA, compared with WT mice.Conclusion
These results suggest that iNKT cells may serve as an adjuvant to enhance Th2 inflammatory response in an OVA-induced murine model of asthma. 相似文献10.
Invariant natural killer T (iNKT) cells are capable of recognizing lipid antigens and secreting Th1/Th2 cytokines. Deficiency
in iNKT cell number or function has been partially implicated in susceptibility to some infectious diseases, such as tuberculosis.
We evaluated iNKT cells in paracoccidioidomycosis, another chronic granulomatous disease endemic in Latin America. iNKT cells
were detected using PBS57-loaded tetramer staining and flow cytometry. Circulating iNKT cell numbers were similar among healthy
individuals who had previously been cured of paracoccidioidomycosis (susceptible individuals, n = 7) and healthy Paracoccidioides brasiliensis-infected (n = 5) and non-infected individuals (n = 5). iNKT from all three groups expanded similarly upon α-GalCer and a synthetic analog (OCH) stimulation. IFN-γ was the
dominant cytokine produced both by ex vivo and by expanded iNKT cells, followed by IL-4 and IL-10, in the three groups. No
deficit in the monocyte expression of CD1d was detected. In conclusion, individuals who had developed paracoccidioidomycosis
in the past have no impairment in iNKT number, expansion capacity, and cytokine secretion. 相似文献
11.
Yong-Sheng Xiao Qiang Gao Xiang-Nan Xu Yi-Wei Li Min-Jie Ju Ming-Yan Cai Chen-Xin Dai Jie Hu Shuang-Jian Qiu Jian Zhou Jia Fan 《PloS one》2013,8(8)
Purpose
To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-γ) in hepatocellular carcinoma (HCC) after curative resection.Experimental Design
Expression of TRAV10, encoding the Vα24 domain of iNKT cells, and IFN-γ mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated.Results
Either intratumoral iNKT cells and IFN-γ alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-γ had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-γand their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-γ, which might be related with more advanced pTNM stage and more vascular invasion.Conclusions
Combination of intratumoral iNKT cells and IFN-γ is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients’ outcome compared with intratumoral iNKT cells or IFN-γ alone. 相似文献12.
Aiden P Corvin 《BMC biology》2011,9(1):1-8
Background
Cytolytic cells of the immune system destroy pathogen-infected cells by polarised exocytosis of secretory lysosomes containing the pore-forming protein perforin. Precise delivery of this lethal hit is essential to ensuring that only the target cell is destroyed. In cytotoxic T lymphocytes (CTLs), this is accomplished by an unusual movement of the centrosome to contact the plasma membrane at the centre of the immunological synapse formed between killer and target cells. Secretory lysosomes are directed towards the centrosome along microtubules and delivered precisely to the point of target cell recognition within the immunological synapse, identified by the centrosome. We asked whether this mechanism of directing secretory lysosome release is unique to CTL or whether natural killer (NK) and invariant NKT (iNKT) cytolytic cells of the innate immune system use a similar mechanism to focus perforin-bearing lysosome release.Results
NK cells were conjugated with B-cell targets lacking major histocompatibility complex class I 721.221 cells, and iNKT cells were conjugated with glycolipid-pulsed CD1-bearing targets, then prepared for thin-section electron microscopy. High-resolution electron micrographs of the immunological synapse formed between NK and iNKT cytolytic cells with their targets revealed that in both NK and iNKT cells, the centrioles could be found associated (or 'docked') with the plasma membrane within the immunological synapse. Secretory clefts were visible within the synapses formed by both NK and iNKT cells, and secretory lysosomes were polarised along microtubules leading towards the docked centrosome. The Golgi apparatus and recycling endosomes were also polarised towards the centrosome at the plasma membrane within the synapse.Conclusions
These results reveal that, like CTLs of the adaptive immune system, the centrosomes of NK and iNKT cells (cytolytic cells of the innate immune system) direct secretory lysosomes to the immunological synapse. Morphologically, the overall structure of the immunological synapses formed by NK and iNKT cells are very similar to those formed by CTLs, with both exocytic and endocytic organelles polarised towards the centrosome at the plasma membrane, which forms a focal point for exocytosis and endocytosis within the immunological synapse. We conclude that centrosomal polarisation provides a rapid, responsive and precise mechanism for secretory lysosome delivery to the immunological synapse in CTLs, NK cells and iNKT cells. 相似文献13.
Background
Invariant NKT (iNKT) cells are regulatory lymphocytes that may be important in disorders with increased Th1 responses. We utilized a 4-year longitudinal observational study of iNKT cells and SLAM signaling pathway factors, which are important for iNKT development in patients with newly diagnosed sarcoidosis.Methods
Detailed clinical, functional, and radiographic evaluation and determination of iNKT peripheral blood cell counts and expression of SLAM signaling factors was carried out at presentation and after 3 months, 1 year, and 4 years of disease follow-up in 29 patients with pulmonary sarcoidosis. At presentation, we also evaluated the frequencies of pulmonary BALF iNKT cells. We also included 37 control subjects.Results
We demonstrated a marked deficiency of blood and lung iNKT cells and decreased expression of SLAM signaling factors in patients with newly diagnosed sarcoidosis. During 4 years of disease follow-up, there was a significant increase in blood iNKT cell numbers and in expression of SLAM signaling factors, mainly SLAMF1, SLAMF6, and FYN. This increase clearly correlated with improvement in patients’ clinical symptoms. At the 4-year endpoint, the disease had gone into remission in the great majority of patients and thus also iNKT cell deficiency. Moreover, at the 4-year endpoint iNKT level reached the iNKT level of the control subjects.Conclusions
Our longitudinal study showed that a disposal of iNKT deficiency in parallel with an increase in expression of SLAM signaling factors characterizes the clinical remission of sarcoidosis. 相似文献14.
恒定自然杀伤T细胞(iNKT)是T淋巴细胞的一个独特亚群,兼具自然杀伤(NK)细胞和T细胞特征,同时表达T细胞受体(TCR)和NK细胞表面标志。iNKT细胞被激活后,通过分泌细胞因子,活化其它免疫细胞参与先天性免疫和获得性免疫,在抗肿瘤免疫过程中发挥调节作用。在多种癌症患者体内,发现外周血中iNKT细胞的数量降低、功能减弱,进而导致临床治疗效果不佳。近年来,基础研究和早期临床试验结果表明,注射抗原递呈细胞或/和体外培养并活化的iNKT细胞,抗肿瘤免疫治疗效果显著。本文就iNKT细胞的分类及生物学特性,在肿瘤免疫治疗中的作用与其机制,以及其临床应用等进行综述。 相似文献
15.
Francesco Ria Romina Penitente Maria De Santis Chiara Nicolò Gabriele Di Sante Massimiliano Orsini Dario Arzani Andrea Fattorossi Alessandra Battaglia Gian Franco Ferraccioli 《Arthritis research & therapy》2008,10(6):R135
Introduction
Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis. 相似文献16.
Introduction
Natural killer (NK) and natural killer T (NKT) cells provide a first line of defense against infection. However, these cells have not yet been examined in patients with Lyme arthritis, a late disease manifestation. Lyme arthritis usually resolves with antibiotic treatment. However, some patients have persistent arthritis after spirochetal killing, which may result from excessive inflammation, immune dysregulation and infection-induced autoimmunity.Methods
We determined the frequencies and phenotypes of NK cells and invariant NKT (iNKT) cells in paired peripheral blood (PB) and synovial fluid (SF) samples from eight patients with antibiotic-responsive arthritis and fifteen patients with antibiotic-refractory arthritis using flow cytometry and cytokine analyses.Results
In antibiotic-responsive patients, who were seen during active infection, high frequencies of CD56bright NK cells were found in SF, the inflammatory site, compared with PB (P <0.001); at both sites, a high percentage of cells expressed the activation receptor NKG2D and the chaperone CD94, a low percentage expressed inhibitory killer immunoglobulin-like receptors (KIR), and a high percentage produced IFN-γ. In antibiotic-refractory patients, who were usually evaluated near the conclusion of antibiotics when few if any live spirochetes remained, the phenotype of CD56bright cells in SF was similar to that in patients with antibiotic-responsive arthritis, but the frequency of these cells was significantly less (P = 0.05), and the frequencies of CD56dim NK cells tended to be higher. However, unlike typical NKdim cells, these cells produced large amounts of IFN-γ, suggesting that they were not serving a cytotoxic function. Lastly, iNKT cell frequencies in the SF of antibiotic-responsive patients were significantly greater compared with that of antibiotic-refractory patients where these cells were often absent (P = 0.003).Conclusions
In patients with antibiotic-responsive arthritis, the high percentage of activated, IFN-γ-producing CD56bright NK cells in SF and the presence of iNKT cells suggest that these cells still have a role in spirochetal killing late in the illness. In patients with antibiotic-refractory arthritis, the frequencies of IFN-γ-producing CD56bright and CD56dim NK cells remained high in SF, even after spirochetal killing, suggesting that these cells contribute to excessive inflammation and immune dysregulation in joints, and iNKT cells, which may have immunomodulatory effects, were often absent. 相似文献17.
Reduced numbers and function of invariant NKT (iNKT) cells partially contribute to type 1 diabetes (T1D) development in NOD
mice. Previous linkage analysis identified a genetic locus on chromosome 2 controlling numbers of thymic iNKT cells. Interestingly,
this locus resides within the Idd13 region that distinguishes NOD mice from the closely genetically related, but strongly T1D-resistant NOR strain. Thus, we
tested if a genetic variant that confers T1D resistance in NOR mice may do so by enhancing iNKT cell numbers. iNKT cells were
enumerated by an α-GalCer analog loaded CD1d tetramer in NOD and NOR mice as well as in NOD stocks carrying NOR-derived congenic
regions on chromosome 1, 2, or 4. Significantly, more thymic and splenic iNKT cells were present in NOR than NOD mice. The
NOR-derived Idd13 region on chromosome 2 contributed the most significant effect on increasing iNKT cell numbers. Subcongenic analyses indicated
that at least two genes within the Idd13 region regulate iNKT cell numbers. These results further define the genetic basis for numerical iNKT cell defects contributing
to T1D development in NOD mice. 相似文献
18.
Pavlína Ptáčková Jan Musil Martin Štach Petr Lesný Šárka Němečková Vlastimil Král Milan Fábry Pavel Otáhal 《Cytotherapy》2018,20(4):507-520
Background aims
Clinical-grade chimeric antigenic receptor (CAR)19 T cells are routinely manufactured by lentiviral/retroviral (LV/RV) transduction of an anti-CD3/CD28 activated T cells, which are then propagated in a culture medium supplemented with interleukin (IL)-2. The use of LV/RVs for T-cell modification represents a manufacturing challenge due to the complexity of the transduction approach and the necessity of thorough quality control.Methods
We present here a significantly improved protocol for CAR19 T-cell manufacture that is based on the electroporation of peripheral blood mononuclear cells with plasmid DNA encoding the piggyBac transposon/transposase vectors and their cultivation in the presence of cytokines IL-4, IL-7 and IL-21.Results
We found that activation of the CAR receptor by either its cognate ligand (i.e., CD19 expressed on the surface of B cells) or anti-CAR antibody, followed by cultivation in the presence of cytokines IL-4 and IL-7, enables strong and highly selective expansion of functional CAR19 T cells, resulting in >90% CAR+ T cells. Addition of cytokine IL-21 to the mixture of IL-4 and IL-7 supported development of immature CAR19 T cells with central memory and stem cell memory phenotypes and expressing very low amounts of inhibitory receptors PD-1, LAG-3 and TIM-3.Conclusions
Our protocol provides a simple and cost-effective method for engineering high-quality T cells for adoptive therapies. 相似文献19.
Yong Xu Zehua Wang Xianhong Du Yuan Liu Xiaojia Song Tixiao Wang Siyu Tan Xiaohong Liang Lifen Gao Chunhong Ma 《Journal of cellular and molecular medicine》2018,22(6):3192-3201
Increased expression of T cell immunoglobulin and mucin domain‐3 (Tim‐3) on invariant natural killer T (iNKT) cells is reported in chronic hepatitis B virus (HBV) infection. However, whether Tim‐3 regulates iNKT cells in chronic HBV condition remains unclear. In this study, our results showed that the expression of Tim‐3 was up‐regulated on hepatic iNKT cells from HBV‐transgenic (Tg) mice or iNKT cells stimulated with α‐galactosylceramide (α‐Galcer). Compared with Tim‐3?iNKT cells, Tim‐3+iNKT cells expressed more IFN‐γ, IL‐4 and CD107a, indicating a strong relationship between Tim‐3 and iNKT cell activation. Constantly, treatment of Tim‐3 blocking antibodies significantly enhanced the production of IFN‐γ, TNF‐α, IL‐4 and CD107a in iNKT cells both in vivo and in vitro. This Tim‐3? mediated suppression of iNKT cells was further confirmed in Tim‐3 knockout (KO) mice. Moreover, Tim‐3 blockade promoted α‐Galcer‐triggered inhibition of HBV replication, displaying as the decreased HBV DNA and HBsAg level in serum, and down‐regulated pgRNA expression in liver tissues. Collectively, our data, for the first time, demonstrated the potential role of Tim‐3 blockade in promoting iNKT cell‐mediated HBV inhibition. Therefore, combination of α‐Galcer with Tim‐3 blockade might be a promising approach in chronic hepatitis B therapy. 相似文献
20.
Marthe C.J. Roex Lois Hageman Matthias T. Heemskerk Sabrina A.J. Veld Ellis van Liempt Michel G.D. Kester Lothar Germeroth Christian Stemberger J.H. Frederik Falkenburg Inge Jedema 《Cytotherapy》2018,20(4):543-555