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Human Leukocyte Antigen-A Allele Distribution in Nasopharyngeal Carcinoma Patients Showing Anti-Melanoma-Associated Antigen A or Synovial Sarcoma X-2 t cell response in Blood

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Chinese Medical Journal 2018年第11期131卷 1289-1295页

作者： Pei-Wen Fan Li Huang Xue-Mei Chang Ya-Ning Feng Xuan Yao Yan-Chun Peng tao Dong Ruo-Zheng Wang Xinjiang Key Laboratory of Oncology The Affiliated Tumor Hospital of Xinjiang Medical University Urumqi Xinjiang 830000 China Department of Radiation Oncology The Affiliated Tumor Hospital of Xinjiang Medical University Urumqi Xinjiang 830000 China CAMS Oxford Center for translation Immunology Chinese Academy of Medical Science Oxford Institute Nuffield Department of Medicine Oxford University Oxford OX3 9DS UK MRC Human Immunology Unit Weatherall Institute of Molecular Medicine Oxford University Oxford OX3 9DS UK

Background： Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma （NPC） patients. In this study, we evaluated the t cell response to melanoma-associated antigen （MAGE）-A1, MAGE-A3, or synovial sarcoma X-2 （SSX-2） in the peripheral blood of treatment-naive NPC patients. the relationship of responses among the three proteins and the human leukocyte antigen （HLA）-A types were analyzed to provide evidence of designing novel therapy. Methods： Sixty-one NPC patients admitted into the tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. the t cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the t cell responses from different groups. Spearman＇s rank correlation was used to analyze the relationship of t cell responses. Results： HLA-A＊02：01, A＊02：07, and A＊24：02 were the three most frequent alleles （18.9%, 12.3%, and 11.5%, respectively） among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific t cell response, respectively. the magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. the t cell response against the three proteins correlated with each other to different extent. the percentage of A＊02：01 and A＊24：02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders. Conclusion： MAGE-A1, MAGE-A3, or SSX-2-specific t cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.

关键词： Human Leukocyte Antigen-A Melanoma-Associated Antigen-A Nasopharyngeal Carcinoma Synovial Sarcoma X-2 t cell response

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Mettl3依赖的m^(6)A甲基化调控CD8^(+)t细胞效应分化和记忆形成

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Science Bulletin 2024年第1期69卷 82-96页

作者：郭文慧王昭张雅娇李亚书杜倩张田田胡瑾姚英鹏张家睿徐迎弟崔晓孙振游孟昊余国涛张好建杜旭光徐靖宇于舒洋 State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China Frontier Science Center for Immunology and Metabolism Medical Research InstituteSchool of MedicineWuhan UniversityWuhan 430071China the Collaborative Innovation Center of tissue Damage Repair and Regeneration Medicine of Zunyi Medical University Zunyi 563000China

Efficient immune responses rely on the proper differentiation of CD8^(+)t cells into effector and memory cells.Here,we show a critical requirement of N^6-Methyladenosine(m^(6)A)methyltransferase Mettl3 during CD8^(+)t cell responses upon acute viral infection.Conditional deletion of Mettl3 in CD8^(+)t cells impairs effector expansion and terminal differentiation in an m^(6)A-dependent manner,subsequently affecting memory formation and the secondary response of CD8^(+)t cells.Our combined RNA-seq and m^(6)AmiCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators.Remarkably,Mettl3 binds to the tbx21 transcript and stabilizes it,promoting effector differentiation of CD8^(+)t cells.Moreover,ectopic expression of t-bet partially restores the defects in CD8^(+)t cell differentiation in the absence of Mettl3.thus,our study highlights the role of Mettl3 in regulating multiple target genes in an m^(6)A-dependent manner and underscores the importance of m^(6)A modification during CD8^(+)t cell response.

关键词： CD8^(+)t cell t cell response Mettl3 m^(6)A Effector Memory

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Synergic effect of NOD1 or NOD2 agonists with tLR3 agonists on murine LSEC to trigger HBV specific t cell response

Synergic effect of NOD1 or NOD2 agonists with TLR3 agonists ...

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第十一届全国免疫学学术大会

作者： Shunmei Huang Gao Xiaoyan Chen Liwen Yang Xilang Zou Shi Du Yanqin Sun Chan Lu Mengji Yang Dongliang Wu Jun Department of Infectious Disease Union Hospital of Tongji Medical CollegeHuazhong University of Science and Technology Department of Virology University Hospital of Essen

Aims:LSEC can switch from a tolerogenic to an immunogenic state and promote the development of t cell immunity.Here,we investigate the effect of LSEC in anti-HBV adaptive immune response,and explored the possibility of NOD1/NOD2-tLR3 agonists as immunomodulatory agents for the treatment of HBV.Methods:CD8+ t cells were isolated from PSM2 HI mice and labeled with CFSE and then cocultured with NOD1(DAP)/NOD2(MDP)/tLR3(Poly(I:C)) stimulated-LSEC for 5 days.the proliferation of CD8+ t cells,the phosphorylation status of NF-k B,MAPK and surface molecules expression in LSEC was detected by FACS.t cells primed by DAP/MDP/Poly(I:C) treated primary LSEC were transferred to the chronic HBV replication mice,serum markers of HBV were assayed by ELICA and q PCR.Results:Stimulation of LSEC with DAP or Poly(I:C) induced the activation of NFκB and MAPK,then significantly upregulated the expression of chemokines,cytokines.Although DAP or Poly(I:C) treated LSEC could not induce the proliferation,but the production of IFN-γ and IL-2 of HBV stimulated CD8+ t cells primed by DAP-or Poly(I:C) treated LSEC.Consistently,a signigcant reduction in HBVDNA,HBs Ag and HBe Ag level occurred in mice received t cells primed by DAP or poly(I:C)-treated LSEC.MDP treatment had no impact on LSEC or HBV-stimulated CD8+ t cells primed by MDP-treated LSEC.Stimulation with DAP or MDP plus Poly(I:C) increased the cytokine(tNF-α,IL-2,CXCL10,CCL5 and CCL8) and surface marker CD54,CD106,CD86 or CD86 expression in LSEC,respectively.DAP or MDP plus Poly(I:C) treated LSEC synergisticallydecreased the levels of HBs Ag,HBe Ag and HBVDNA.Conclusion:the combinatory stimulation with DAP or MDP plus Poly(I:C) in vitro could synergistically render LSEC maturation and activate HBV specific t cells responses.this is a particular relevance for the regulation of the local innate immune response against HBV infections.

关键词： innate immunity LSEC t cell response HBV

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SARS-CoV-2-specific t cell responses wane profoundly in convalescent individuals 10 months after primary infection

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Virologica Sinica 2023年第4期38卷 606-619页

作者： Ziwei Li tiandan Xiang Boyun Liang Jing Liu Hui Deng Xuecheng Yang Hua Wang Xuemei Feng Gennadiy Zelinskyy Mirko trilling Kathrin Sutter Mengji Lu Ulf Dittmer Baoju Wang Dongliang Yang Xin Zheng Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Institute for Virology University Hospital of EssenUniversity of Duisburg-EssenEssen45147Germany Joint International Laboratory of Infection and Immunity Huazhong University of Science and TechnologyWuhan430022China

A key question in the coronavirus disease 2019(COVID-19)pandemic is the duration of specific t cell responses against the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)post primary infection,which is difficult to address due to the large-scale COVID-19 vaccination and re-exposure to the virus.Here,we conducted an analysis of the long-term SARS-CoV-2-specific t cell responses in a unique cohort of convalescent individuals(CIs)that were among the first to be infected worldwide and without any possible antigen re-exposure since then.the magnitude and breadth of SARS-CoV-2-specific t cell responses correlated inversely with the time that had elapsed from disease onset and the age of those CIs.the mean magnitude of SARS-CoV-2-specific CD4 and CD8 t cell responses decreased about 82%and 76%,respectively,over the time period of ten months after infection.Accordingly,the longitudinal analysis also demonstrated that SARS-CoV-2-specific t cell responses waned significantly in 75%of CIs during the follow-up.Collectively,we provide a comprehensive characterization of the long-term memory t cell response in CIs,suggesting that robust SARS-CoV-2-specific t cell immunity post primary infection may be less durable than previously expected.

关键词： COVID-19 SARS-CoV-2 t cell response Convalescence

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Efficacy of Heshouwu(Radix Polygoni Multiflori)on gut mircobiota in mice with autoimmune encephalomyelitis

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中医杂志:英文版 2023年第4期43卷 676-685页

作者： ZHOU Jun WANG Junhua LI Xiaobing WAN Chenyi LI Fangjun LüYanni CHEN Hao SUN Meiying Department of Chinese Medicine Gaoxin Branch of the First Affiliated Hospital of Nanchang UniversityNanchang 330000China Department of Neurology Gaoxin branch of the First Affiliated Hospital of Nanchang UniversityNanchang 330000China Department of Pharmacy Gaoxin branch of the First Affiliated Hospital of Nanchang UniversityNanchang 330000China

OBJECtIVE:to learn the mechanisms between gut microbiome and the autoimmunity benefits on traditional Chinese Medicine(tCM)in central nervous system(CNS),we investigated the neuro-protection effects and gut mircobiota changes of Heshouwu(Radix Polygoni Multiflori)on experimental autoimmune encephalomyelitis(EAE),an animal model of multiple sclerosis(MS).MEtHODS:Mice were randomly divided into four groups:EAE mice(control phosphate-buffered saline group),50 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,100 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice,and 200 mg·kg^(-1)·d^(-1)Heshouwu(Radix Polygoni Multiflori)-treated EAE mice.the spinal cords were stained with hematoxylin and eosin(HE)and luxol fast blue for evaluating inflammatory infiltration and demyelination.the percentages of granulocyte macrophage-colony stimulating factor(GM-CSF)+CD4+,interleukin 17(IL-17)+CD4+,Foxp3 CD4+,and interferon-γ(IFN-γ)+CD4+t cells in the inguinal lymph nodes(LNs)and brain were determined by flow cytometry analysis.16S rRNA gene sequencing was employed to analyze the changes in gut microbiota.RESULtS:We found that Heshouwu(Radix Polygoni Multiflori)alleviated the disease severity and neuropathology of EAE as evaluated by clinical and histopathologyical scores.Heshouwu(Radix Polygoni Multiflori)increased the diversity and abundance of the gut microbiota,and decreased Firmicutes/Bacteroidetes ratio(F/B ratio).Heshouwu(Radix Polygoni Multiflori)also decreased the concentrations of IL-10,and IL-21 and increase the levels of GM-CSF,IL-17A,IL-17F and IL-22 in serum of EAE mice.Moreover,Heshouwu(Radix Polygoni Multiflori)modulated the t cell responses by inhibiting th17 cells and restoring treg cells in the small intestine lymphoid tissues and inguinal lymph nodes.Microbiota-depleted mice receiving Heshouwu(Radix Polygoni Multiflori)-treated fecal microbiota transplantation had lower disease severity,neuropathology scores and alleviation of th17/treg imbalance compared to ad libitum group.

关键词： gastrointestinal microbiome encephalomyelitis autoimmune experimental Heshouwu(Radix Polygoni Multiflori) t cell response

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Natural course of chronic hepatitis B is characterized by changing patterns of programmed death type-1 of CD8-positive t cells

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World Journal of Gastroenterology 2010年第5期16卷 618-624页

作者： Liang, Xue-Song Zhou, Ying Li, Chen-Zhong Wan, Mo-Bin Second Mil Med Univ Changhai Hosp Dept Infect Dis Shanghai 200433 Peoples R China Second Mil Med Univ Dept Biochem & Mol Biol Shanghai 200433 Peoples R China

AIM:to investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. MEtHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total t cells was detected by flow cytometry.Levels of total CD8+t cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULtS:the PD-1 expression in t cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the t-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the t-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in t cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:the PD-l/PD-L1 pathway plays a different role in t-cell response during the natural course of chronic HBV infection.

关键词： Programmed death type-1 Hepatitis B virus Chronic hepatitis B Natural stage CD8+t cell Serum viral load Programmed death ligand t cell response

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Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

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Fundamental Research 2021年第2期1卷 124-130页

作者： Airu Zhu Zhao Chen Yanqun Wang Qiuhui Zeng Jing Sun Zhen Zhuang Fang Li Jingxian Zhao Jincun Zhao Nanshan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China

the coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represents a major public health threat worldwide.Insight into protective and pathogenic aspects of SARS-CoV-2 immune responses is critical to work out effective therapeutics and develop vaccines for controlling the disease.Here,we review the present literature describing the innate and adaptive immune responses including innate immune cells,cytokine responses,antibody responses and t cell responses against SARS-CoV-2 in human infection,as well as in AEC2-humanized mouse infection.We also summarize the now known and unknown about the role of the SARS-CoV-2 immune responses.By better understanding the mechanisms that drive the immune responses,we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.

关键词： SARS-CoV-2 Innate immune response Humoral immune responses t cell response Mouse model

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