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Cellular & Molecular Immunology 2022年第10期19卷 1073-1076页

作者： Junqiong Huang Scot Leary jim xiang Cancer Research Cluster Saskatchewan Cancer AgencySaskatoonSKCanada Department of Oncology College of MedicineUniversity of SaskatchewanSaskatoonSKCanada Department of Blood Transfusion Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhouChina Department of Biochemistry Microbiology and ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSKCanada

CD8^(+)effector T(T_(E))cells play a critical role in immunity against *** response to a pathogenic stimulus,antigenpresenting cells(APCs)deliver three signals[via T-cell receptor(TCR),costimulation,and cytokines]to naive CD8^(+)T cells,stimulating their entry into a developmental program characterized by T-cell expansion followed by a contraction *** the contraction phase,90-95%of IL-7R^(-)CD62L^(-)KLRG1^(+)T_(E)cells undergo cell apoptosis.

关键词： FOXO1 immunity stimulation

Author Correction:Distinct strengths of mTORC1 control T-cell memory via transcriptional FOXO1 and metabolic AMPKa1 pathways in linear cell differentiation and asymmetric cell division models

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Cellular & Molecular Immunology 2023年第3期20卷 311-312页

作者： Junqiong Huang Scot Leary jim xiang Cancer Research Cluster Saskatchewan Cancer Agency Saskatoon SK Canada Department of Oncology College of Medicine University of Saskatchewan Saskatoon SK Canada Department of Blood Transfusion Affiliated Hospital of Zunyi Medical University Zunyi Guizhou China Department of Biochemistry Microbiology and Immunology College of Medicine University of Saskatchewan Saskatoon SK Canada

In the version of this article initially published,unintended typographical errors in the original version of Fig.1B were made during manuscript *** revised Fig.1,including the correct Fig.1B,isshown below.

关键词： FOXO1 mTORC1 initially

Defect of CD8+ Memory T Cells Developed in Absence of IL-12 Priming for Secondary Expansion

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Cellular & Molecular Immunology 2008年第2期5卷 147-152页

作者： Terence Moyana jim xiang Department of Pathology University of OttawaOntario K1H 8L6Canada Department of Oncology University of SaskatchewanSaskatoonSaskatchewan S7N 4H4Canada

IL-12 priming plays an important role in stimulation of CD8+ effector T cells and development of CD8+ memory T (Tm) cells. However,the functional alteration of CD8+ Tm cells developed in the absence of IL-12 priming is elusive. In this study,we investigated the capacity of secondary expansion of CD8+ Tm cells developed from transgenic OT I CD8+ T cells. The latter cells were in vitro and in vivo stimulated by ovalbumin (OVA)-pulsed dendritic cells DCOVA and (IL-12-/-)DCOVA derived from wild-type C57BL/6 and IL-12 gene knockout mice,respectively. We demonstrated that IL-12 priming is important not only in CD8+ T cell clonal expansion,but also in generation of CD8+ Tm cells with the capacity of secondary expansion upon antigen re-encounter. However,IL-12 signaling is not involved in CD8+ Tm cell survival and recall responses. Therefore,this study provides useful information for vaccine design and development.

关键词： IL-12 effector CD8+ T cell memory T cell recall response

Combinational adenovirus-mediated gene therapy and dendritic cell vaccine in combating well-established tumors

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Cell Research 2006年第3期16卷 241-259页

作者： Terence Moyana jim xiang Department of Pathology and Laboratory Medicine University of OttawaOttawaOntario K1H 8L6Canada Research Unit Health Research DivisionSaskatchewan Cancer AgencyDepartments of Oncology.Microbiology and Immunology.University of Saskatchewan20 Campus DriveSaskatoonSaskatchewan STN 4H4Canada

Recent developments in tumor immunology and biotechnology have made cancer gene therapy and *** current efforts for cancer gene therapy mainly focus on using immunogenes,chemogenes and tumor sup-pressor *** to all these therapies is the development of efficient vectors for gene *** far,adenovirus(AdV)-mediated gene therapy is one of the most promising approaches,as has confirmed by studies relating to animaltumor models and clinical *** cells (DCs) are highly efficient,specialized antigen-presenting cells,and DC-based tumor vaccines are regarded as having much potential in cancer *** with DCs pulsedwith tumor peptides,Iysates,or RNA,or loaded with apoptotic/necrotic tumor cells,or engineered to express certaincytokines or chemokines could induce significant antitumor cytotoxic T lymphocyte (CTL) responses and *** both AdV-mediated gene therapy and DC vaccine can both stimulate antitumor immune responses,their therapeutic efficiency has been limited to generation of prophylactic antitumor immunity against re-challenge withthe parental tumor cells or to growth inhibition of small ***,this approach has been unsuccessful in com-bating welt-established tumors in animal ***,a major strategic goal of current cancer immunotherapy hasbecome the development of novel therapeutic strategies that can combat welt-established tumors,thus resembling realclinical practice since a good proportion of cancer patients generally present with significant *** this paper,wereview the recent progress in AdV-mediated cancer gene therapy and DC-based cancer vaccines,and discuss combinedimmunotherapy including gene therapy and DC *** underscore the fact that combined therapy may have someadvantages in combating well-established tumors vis-a-vis either modality administered as a monotherapy.

关键词： gene therapy adenovirus dendritic cells vaccine cytotoxic T lymphocytes antitumor immunity

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

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Cellular & Molecular Immunology 2008年第4期5卷 261-269页

作者： Khawaja Ashfaque Ahmed Manjunatha Ankathatti Munegowda jim xiang Research Unit Saskatchewan Cancer AgencyDepartments of OncologyMicrobiology and ImmunologyCollege of MedicineUniversity of Saskatchewan20 Campus DriveSaskatoon Saskatchewan S7N 4H4Canada Research Unit Saskatchewan Cancer AgencyDepartments of OncologyMicrobiology and ImmunologyCollege of MedicineUniversity of Saskatchewan20 Campus Drive SaskatoonSaskatchewan S7N 4H4Canada

Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular ＆ Molecular Immunology. 2008;5（4）：261-269.

关键词： cellular interaction membrane molecule transfer CTL response immune suppression

Acquired pMHC I Complexes Greatly Enhance CD4^+ Th Cell's Stimulatory Effect on CD8^+ T Cell-Mediated Diabetes in Transgenic RIP-mOVA Mice

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Cellular & Molecular Immunology 2008年第6期5卷 407-415页

作者： Khawaja Ashfaque Ahmed Yufeng Xie Xueshu Zhang jim xiang Research Unit Saskatchewan Cancer Agency Departments of OncologyMicrobiology and Immunology College of Medicine University ofSaskatchewan 20 Campus Drive Saskatoon Saskatchewan S7N 4H4Canada Ahmed and Xie made the same contribution to the study

CD4＋ helper T （Th） cells play pivotal roles in induction of CD8＋ CTL immunity. However, the mechanism of CD4＋ T cell help delivery to CD8＋ T cells in vivo is still elusive. In this study, we used ovalbumin （OVA）-pulsed dendritic cells （DCovA） to activate OT-II mouse CD4＋ T cells, and then studied the help effect of these CD4＋ T cells on CD8＋ cytotoxic T lymphocyte （CTL） responses＋ We also examined CTL mediated islet β cell destruction which leaded to diabetes in wild-type C57BL/6 mice and transgenic rat insulin promoter （RIP）-mOVA mice expressing β cell antigen OVA with self OVA-specific tolerance, respectively. In adoptive transfer experiments, we demonstrated that help, in the form of peptide/major histocompatibility complex （pMHC） I acquired from DCovA by DCovA activation, was required for induction of OVA-specific CTL responses in C57BL/6 mice. However, in combination ＋＋＋ with TCR transgenlc OT-I mouse CD8 T ceils, the tolerogenic dosage of CD4＋ Th cells with acquired pMHC I, but not CD4＋（Kb-/-） Th cells without acquired pMHC I were able to cause diabetes in 8/10 （80%） RIP-mOVA mice. This study thus expands the current knowledge in T cell-mediated autoimmunity and provides insight into the nature of CD4＋ T cell-mediated help in CD8＋ CTL induction. Cellular ＆ Molecular Immunology. 2008;5（6）：407-415.

关键词： CD4+ Th pMHC 1 dendritic cell membrane acquisition diabetes

Mannose-6-phosphate receptor: a novel regulator of T cell immunity

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Cellular & Molecular Immunology 2018年第11期15卷 986-988页

作者： Anjuman Ara Khawaja Ashfaque Ahmed jim xiang Cancer Research Cluster Saskatchewan Cancer AgencySaskatoonSKCanada Division of Oncology College of MedicineUniversity of SaskatchewanSaskatoonSKCanada

CD8^(+) cytotoxic T cells(CTLs)protect against pathogens and cancer.1,2,3,4 Over the past few years,CTL responses have been extensively studied.1,2,3,4 In response to an infection,the CTL response develops in three phases:expansion,contraction,and memory.2,3,In the expansion phase,pathogen-derived antigens(Ags)trigger activation and proliferation of Ag-specific CTLs,leading to the generation of effector CTLs(eCTLs)with cytotoxic functions.2,5,Later,in the contraction phase,90–95%of eCTLs die as a result of activation-induced cell apoptosis.

关键词： immunity cytotoxic functions.

Dendritic Cell-Derived Exosomes Stimulate Stronger CD8^+ CTL Responses and Antitumor Immunity than TVimor Cell-Derived Exosomes

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Cellular & Molecular Immunology 2006年第3期3卷 205-211页

作者： Siguo Hao Ou Bai Jinying Yuan Mabood Qureshi jim xiang Research Unit Division of Health Research Saskatchewan Cancer Agency Departments of Oncology Immunology and Pathology College of Medicine University of Saskatchewan Saskatoon Saskatchewan STN 4H4 Canada Siguo Hao and Ou Bai made the same contribution in this study

Exosomes （EXO） derived from dendritic cells （DC） and tumor cells have been used to stimulate antitumor immune responses in animal models and in clinical trials. However, there has been no side-by-side comparison of the stimulatory efficiency of the antitumor immune responses induced by these two commonly used EXO vaccines. In this study, we selected to study the phenotype characteristics of EXO derived from a transfected EG7 tumor cells expressing ovalbumin （OVA） and OVA-pulsed DC by flow cytometry. We compared the stimulatory effect in induction of OVA-specific immune responses between these two types of EXO. We found that OVA protein-pulsed DCOVA-derived EXO （EXODC） can more efficiently stimulate naive OVA-specific CD8^＋ T cell proliferation and differentiation into cytotoxic T lymphocytes in vivo, and induce more efficient antitumor immunity than EG7 tumor cell-derived EXO （EXOEG7）. In addition, we elucidated the important role of the host DC in EXO vaccines that the stimulatory effect of EXO is delivered to T cell responses by the host DC. Therefore, DC-derived EXO may represent a more effective EXO-based vaccine in induction of antitumor immunity. Cellular ＆ Molecular Immunology. 2006;3（3）：205-211.

关键词： dendritic cell exosome tumor cell cytotoxic T lymphocyte antitumor immunity

Interferon γ Stimulates Cellular Maturation of Dendritic Cell Line DC2.4 Leading to Induction of Efficient Cytotoxic T Cell Responses and Antitumor Immunity

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Cellular & Molecular Immunology 2007年第2期4卷 105-111页

作者： Tianpei He Chaoke Tang Shulin Xu Terence Moyana jim xiang Research Unit Health Research Division Saskatchewan Cancer Agency Departments of Oncology and Immunology University of Saskatchewan Saskatoon Saskatchewan S7N 4H4 Canada Department of Pathology and Laboratory Medicine University of Ottawa Ontario Canada

Dendritic cells （DCs） are the most potent antigen-presenting cells （APCs） for the initiation of antigen （Ag）-specific immune responses. In most studies, mature DCs are generated from bone marrow cells or peripheral monocytes; in either case, the harvested cells are then cultured in medium containing recombinant GM-CSF, IL-4 and TNF-α for 7-10 days and stimulated with lipopolysaccharide （LPS）. However, this approach is time-consuming and expensive. There is another less cost approach of using immobilized DC cell lines, which can easily grow in the medium. A disadvantage with the immobilized DC cell lines, however, is that they are immature DCs and lack expression of MHC class Ⅱ and costimulatory CD40 and CD80 molecules. This, therefore, limits their capacity for inducing efficient antitumor immunity. In the current study, we investigated the possible efficacy of various stimuli （IL-1β, IFN-γ, TNF-α CpG and LPS） in converting the immature dendritic cell line DC2.4 to mature DCs. Our findings were quite interesting since we demonstrated for the first time that IFN-γ was able to stimulate the maturation of DC2.4 cells. The IFN-γ-activated ovalbumin （OVA）-pulsed DC2.4 cells have capacity to upregulate MHC class Ⅱ, CD40, CD80 and CCR7, and to more efficiently stimulate in vitro and in vivo OVA-specific CD8^＋ T cell responses and antitumor immunity. Therefore, IFN-γ-activated immortal DC2.4 ceils may prove to be useful in the study of DC biology and antitumor immunity.

关键词： IFN-γ DC2.4 line DC maturation CTL antitumor immunity

Transgenic 4-1BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via increased priming of CD44＋CD62Lhigh IL-7R＋ CTLs with up- and downregulation of anti- and pro-apoptosis genes

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Cellular & Molecular Immunology 2015年第4期12卷 456-465页

作者： Rong Wang Andrew Freywald Yue Chen Jianqing Xu Xin Tan jim xiang Cancer Research Unit Saskatchewan Cancer Agency Saskatoon Saskatchewan Canada Department of Oncology University of Saskatchewan Saskatoon Saskatchewan Canada Department of Pathology University of Saskatchewan Saskatoon Saskatchewan Canada Department of Epidemiology and Community Health University of Ottawa Canada Shanghai Public Health Clinical Center Fudan University Shanghai China School of Life Science Beijing Institute of Technology Beijing China

Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/*** vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of st

关键词： 4-1BBL Gag HLA-A2 mice T cell-based vaccine therapeutic immunity