Lianxian Cui

Chinese Academy of Medical Sciences & Peking Union Medical College

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Wei He

Chinese Academy of Medical Sciences & Peking Union Medical College

Denian Ba

Chinese Academy of Medical Sciences & Peking Union Medical College

Wei He

Guangzhou University of Chinese Medicine

Yu Hu

Cell Technology (China)

Jianmin Zhang

Chinese Academy of Medical Sciences & Peking Union Medical College

Chi Ma

University of Utah

Xueyan Xi

Hubei University of Medicine

Kang Ning

Chinese Academy of Medical Sciences & Peking Union Medical College

Huiyuan Zhang

Sichuan University

Wei Cao

The University of Texas Health Science Center at Houston

Cooperative Institutions

Chinese Academy of Medical Sciences & Peking Union Medical College

Peking Union Medical College Hospital

Capital Medical University

Sun Yat-sen University

Fudan University

Shanghai Jiao Tong University

State Key Laboratory of Medical Molecular Biology

Zhejiang University

Chinese Academy of Sciences

Peking University

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Global Characterization of Differential Gene Expression Profiles in Mouse Vγ1+ and Vγ4+ γδ T Cells

PLoS ONE (2014)

Peng Dong Siya Zhang Menghua Cai Kang Ning Yu Hu

Peripheral γδ T cells in mice are classified into two major subpopulations, Vγ1+ and Vγ4+, based on the composition of T cell receptors. However, their intrinsic differences remain unclear. In this study, we analyzed gene expression profiles of the two subsets using Illumina HiSeq 2000 Sequencer. We identified 1995 transcripts related to the activation of Vγ1+ γδ T cells, and 2158 transcripts related to the activation of Vγ4+ γδ T cells. We identified 24 transcripts differentially expressed between the two subsets in resting condition, and 20 after PMA/Ionomycin treatment. We found that both cell types maintained phenotypes producing IFN-γ, TNF-α, TGF-β and IL-10. However, Vγ1+ γδ T cells produced more Th2 type cytokines, such as IL-4 and IL-5, while Vγ4+ γδ T cells preferentially produced IL-17. Our study provides a comprehensive gene expression profile of mouse peripheral Vγ1+ and Vγ4+ γδ T cells that describes the inherent differences between them.

Ionomycin

10.1371/journal.pone.0112964

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Citations (14)

Efficient augmentation of a long-lasting immune responses in HIV-1 gag DNA vaccination by IL-15 plasmid boosting

Vaccine (2008)

Wenjing Li Shirui Li Yu Hu Bixia Tang Lianxian Cui

Boosting

Immune Recognition

10.1016/j.vaccine.2008.03.081

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Citations (23)

γδ T Cells Provide Protective Function in Highly Pathogenic Avian H5N1 Influenza A Virus Infection

Frontiers in Immunology (2018)

Peng Dong Xiangwu Ju Yiwu Yan Siya Zhang Menghua Cai

Given the high mortality rate (>50%) and potential danger of intrapersonal transmission, highly pathogenic avian influenza (HPAI) H5N1 epidemics still pose a significant threat to humans. γδ T cells, which participate on the front line of the host immune defense, demonstrate both innate, and adaptive characteristics in their immune response and have potent antiviral activity against various viruses. However, the roles of γδ T cells in HPAI H5N1 viral infection remain unclear. In this study, we found that γδ T cells provided a crucial protective function in the defense against HPAI H5N1 viral infection. HPAI H5N1 viruses could directly activate γδ T cells, leading to enhanced CD69 expression and IFN-γ secretion. Importantly, we found that the trimer but not the monomer of HPAI H5N1 virus hemagglutinin (HA) proteins could directly activate γδ T cells. HA-induced γδ T cell activation was dependent on both sialic acid receptors and HA glycosylation, and this activation could be inhibited by the phosphatase calcineurin inhibitor cyclosporin A but not by the phosphatidylinositol 3-kinase (PI3-K) inhibitors wortmannin and LY294002. Our findings provide a further understanding the mechanism underlying γδ T cell-mediated innate and adoptive immune responses against HPAI H5N1 viral infection, which helps to develop novel therapeutic strategies for the treatment of H5N1 infection in the future.

Highly pathogenic

10.3389/fimmu.2018.02812

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Citations (34)

Distinct pattern of human Vdelta1 gammadelta T cells recognizing MICA.

Cellular and Molecular Immunology (2005)

Jianqiang Li Lianxian Cui Wei He

NKG2D

CD1

ZAP70

Source

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Citations (17)

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Cellular and Molecular Immunology (2011)

Jianhua Zhou Ning Kang Lianxian Cui Denian Ba Wei He

Adoptive Cell Transfer

10.1038/cmi.2011.16

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Citations (59)

Four novel ULBP splice variants are ligands for human NKG2D

International Immunology (2008)

Wei Cao Xueyan Xi Zhun Wang Liling Dong Zhiyong Hao

UL16-binding proteins [ULBPs, also termed as retinoic acid early transcripts (RAET1) molecules] are frequently expressed by malignant transformed cells and stimulate anti-tumor immune responses mediated by NKG2D-positive NK cells, CD8+ αβ T cells and γδ T cells in vitro and in vivo. In this study, we identified four novel functional splice variants of ULBPs including ULBP4-I, ULBP4-II, ULBP4-III and RAET1G3 in HepG2 liver carcinoma cells, WISH human amnion cells, Hep-2 larynx carcinoma cells and K562 leukemia cells, respectively, by reverse transcription–PCR and T vector cloning strategy. Analysis of alignments of amino acid sequences of the splice variants illustrated that there were important modifications between splice variants and their individual parental ULBP. All ULBP4 splice variants (ULBP4-I, ULBP4-II and ULBP4-III) were type 1 membrane-spanning molecules and had the ability to bind with human NKG2D receptor in vitro. Ectopic expressions of ULBP4 and ULBP4 splice variants resulted in the enhanced cytotoxic sensitivity of target cells against NK cells, which could be blocked by anti-NKG2D mAb. Moreover, co-culture-free soluble forms of ULBP4 splice variants (their α1 + α2 ectodomains) and RAET1G3 (soluble splice variant of RAET1G2) with NK cells down-regulated the cell surface expression of NKG2D. Finally, immobilized in a plate-bound form of RAET1G3 stimulated NK cells to secrete IFN-γ. Taken together, all the identified functional splice variants will help to advance our knowledge regarding the overall functions of ULBP gene family.

NKG2D

splice

10.1093/intimm/dxn057

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Citations (28)

Identification of Human T Cell Receptor γδ-recognized Epitopes/Proteins via CDR3δ Peptide-based Immunobiochemical Strategy

Journal of Biological Chemistry (2008)

Hui Chen Xiaojuan He Zhun Wang Di Wu Huiyuan Zhang

Human T lymphocytes, bearing T cell receptor (TCR) gammadelta, play an important role in anti-tumor/microbe immune responses. However, few tumor antigens recognized by TCRgammadelta have been defined so far. To investigate antigenic epitopes/proteins recognized by gammadeltaT cells, we have established a new immunobiochemical strategy that uses complementarity-determining region 3 of TCR delta chain (CDR3delta) peptide-mediated epitope/protein-binding assays. CDR3delta peptides synthesized using the CDR3 region in TCR Vdelta2 chain were validated for their binding specificity to target cells or tissues. These CDR3delta peptides were then employed as probes to pan putative epitopes in a 12-mer random peptide phage-displayed library and to identify putative protein ligands within tumor protein extracts by affinity chromatography and liquid chromatography/electrospray ionization-tandem mass spectrometry analysis. As a result, we have identified nine peptides and two proteins for TCRgammadelta, including human mutS homolog 2 (hMSH2) and heat shock protein (HSP) 60. All nine tested epitope peptides not only bind to gammadeltaT cells but also functionally activate gammadeltaT cells in vitro. Identification of HSP60 confirms the validity of this method as HSP60 is an identified ligand for TCRgammadelta. We show that hMSH2 is expressed on the surface of SKOV3 tumor cells, and cytotoxicity of Vdelta2 gammadeltaT cells to SKOV3 cells was blocked by anti-hMSH2 antibody, suggesting that hMSH2 may be a new ligand for TCRgammadelta. Taken together, our findings provide a novel immunobiochemical strategy to identify epitopes/proteins recognized by gammadeltaT cells.

HSP60

Linear epitope

10.1074/jbc.m708067200

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Citations (63)

Rwdd1, a Thymus Aging Related Molecule, Is a New Member of the Intrinsically Unstructured Protein Family

Cellular and Molecular Immunology (2008)

Kang Ning Chen Dai Li Wang Lian Duan Shirong Liu

Proteolysis

Protein family

Family member

Sequence (biology)