CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

Zhao, Hui; Xi, Xueyan; Cui, Lianxian; Wang, He

doi:10.1038/cmi.2011.28

Cited by 21 publications

(12 citation statements)

References 37 publications

(42 reference statements)

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“…Ectopically expressed hMSH2 in a malignant environment, including virus infection, oxidative stress, and tumorigenesis, created a signal alerting the immune system in immunosurveillance via ␥␦ T cells (14,15). Further, engineered antibodies, based on the CDR3␦ sequence, showed tumor binding specificity and antitumor effects in mouse xenograft models (19,20). In this study, we demonstrated that a novel autoimmune disease-associated antigen CCT6A is recognized by ␥␦ T cells.…”

Section: Discussionmentioning

confidence: 74%

Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases

Chen

You

Wang

et al. 2016

Journal of Biological Chemistry

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Human γδ T cells recognize conserved endogenous and stress-induced antigens typically associated with autoimmune diseases. However, the role of γδ T cells in autoimmune diseases is not clear. Few autoimmune disease-related antigens recognized by T cell receptor (TCR) γδ have been defined. In this study, we compared Vδ2 TCR complementarity-determining region 3 (CDR3) between systemic lupus erythematosus (SLE) patients and healthy donors. Results show that CDR3 length distribution differed significantly and displayed oligoclonal characteristics in SLE patients when compared with healthy donors. We found no difference in the frequency of Jδ gene fragment usage between these two groups. According to the dominant CDR3δ sequences in SLE patients, synthesized SL2 peptides specifically bound to human renal proximal tubular epithelial cell line HK-2; SL2-Vm, a mutant V sequence of SL2, did not bind. We identified the putative protein ligand chaperonin-containing T-complex protein 1 subunit ζ (CCT6A) using SL2 as a probe in HK-2 cell protein extracts by affinity chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. We found CCT6A expression on the surface of HK-2 cells. Cytotoxicity of only Vδ2 γδ T cells to HK-2 cells was blocked by anti-CCT6A antibody. Finally, we note that CCT6A concentration was significantly increased in plasma of SLE and rheumatoid arthritis patients. These data suggest that CCT6A is a novel autoantigen recognized by Vδ2 γδ T cells, which deepens our understanding of mechanisms in autoimmune diseases.

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Section: Discussionmentioning

confidence: 74%

Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases

Chen

You

Wang

et al. 2016

Journal of Biological Chemistry

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“…Although they represent only a small population of immune cells, cd-T cells exhibit features characteristic of both innate and adaptive immunity and play an indispensable role in host defense, immune surveillance and homeostasis. [1][2][3][4] In humans, cd-T cells constitute approximately 1%-5% of circulating T cells, and most of them bear the Vc9Vd2 T-cell receptor (TCR). 5,6 Human Vc9Vd2-T cells can be specifically activated in an HLA-unrestricted manner by small non-peptidic phosphoantigens, which are metabolites of the isoprenoid biosynthesis pathways.…”

Section: Introductionmentioning

confidence: 99%

Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

Xiang

Feng

et al. 2013

Cell Mol Immunol

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γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin-granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas-Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus.

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“…7,8 Vc9Vd2-T cells are the major cd-T-cell population in peripheral blood in humans, and these cells exhibit characteristics of both innate and adaptive immune responses. [9][10][11] It has been shown that human Vc9Vd2-T cells have antiviral activity against different viruses, including influenza virus, through cytolytic and non-cytolytic mechanisms. [12][13][14][15] Vc9Vd2-T cells can directly kill influenza virus-infected cells through the release of perforin and granzyme B.…”

Section: Introductionmentioning

confidence: 99%

Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates

Mao

et al. 2013

Cell Mol Immunol

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Preterm and small-for-gestational-age (SGA) neonates are vulnerable groups that are susceptible to various microbial infections. Vc9Vd2-T cells are critical components of the host immune system and have been demonstrated to play an important role in the defense against viral infection in adults. However, the characteristics of Vc9Vd2-T cells in children, especially the preterm and SGA populations, are poorly understood. Here, we examined the frequency and antiviral function of Vc9Vd2-T cells in neonates, including preterm, SGA and full-term babies. When compared to adults, neonates had a significantly lower percentage of Vc9Vd2-T cells in the blood. Upon influenza virus stimulation, neonatal Vc9Vd2-T cells, especially from preterm and SGA babies, showed markedly decreased and delayed antiviral cytokine responses than those of adults. In addition, the antiviral responses of neonatal Vc9Vd2-T cells were positively correlated with gestational age and birth weight. Finally, a weaker expansion of Vc9Vd2-T cells by isopentenyl pyrophosphate (IPP) was shown in neonates than the expansion in adults. Our data suggest that the depressed antiviral activity and decreased frequency of Vc9Vd2-T cells may likely account for the high susceptibility to microbial infection in neonates, particularly in preterm and SGA babies. Improving Vc9Vd2-T-cell function of neonates may provide a new way to defend against virus infection.

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CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

Cited by 21 publications

References 37 publications

Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases

Chaperonin-containing T-complex Protein 1 Subunit ζ Serves as an Autoantigen Recognized by Human Vδ2 γδ T Cells in Autoimmune Diseases

Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

Vγ9Vδ2-T lymphocytes have impaired antiviral function in small-for-gestational-age and preterm neonates

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