Mycobacterium Vaccae Regulate γδT17 and γδTreg Cells in Mice Asthmatic Lung

Background Dysregulation of the balance between different T cell populations is believed to be an important basis for asthma.Objective To observe the changes in γδT subtypes in transgenic asthmatic mice after aerosol inhalation of Mycobacterium vaccae, and to further investigate the mechanism of M. vaccae in asthmatic mice and its relationship with γδT cells.Methods TCR-β-/- mice were exposed to atomized normal saline or M. vaccae for 5 days and the γδT cells from the lung tissues were isolated. Changes in γδT17 and γδTreg populations were detected. Asthma was induced in BALB/c mice using ovalbumin, which was then transplanted with control or M. vaccae-primed γδT cells. First we analyzed the content of γδT cells that secrete IL-17 (IL-17 γδT cells) and Foxp3+ γδT cells in lung tissues and then measured the content of IL-17 in the bronchoalveolar lavage fluid (BALF) by ELISA.Results Exposure to M. vaccae increased and decreased the relative proportions of Foxp3+ γδT cells and IL-17+ γδT cells, respectively, thereby decreasing airway reactivity and inflammation levels in asthmatic mice, and significantly decreasing IL-17 levels in BALF. Furthermore, mice treated with these primed T cells showed a decrease in IL-17+ γδT cells, and a concomitant increase in Foxp3+ γδT cells in their lung tissues. Furthermore, adoptive transfer of M. vaccae-primed γδT cells decreased GATA3 and NICD and increased T-bet in lung.Conclusions The M. vaccae-primed γδT cells alleviated the symptoms of asthma by reversing Th2 polarization in the lungs and inhibiting the Notch/GATA3 pathway.     

Redirecting αβ T cells against cancer cells by transfer of a broadly tumor-reactive γδT-cell receptor

Major limitations of currently investigated αβT cells redirected against cancer by transfer of tumor-specific αβTCR arise from their low affinity, MHC restriction, and risk to mediate self-reactivity after pairing with endogenous α or βTCR chains. Therefore, the ability of a defined γ9δ2TCR to redirect αβT cells selectively against tumor cells was tested and its molecular interaction with a variety of targets investigated. Functional analysis revealed that a γ9δ2TCR efficiently reprograms both CD4(+) and CD8(+) αβT cells against a broad panel of cancer cells while ignoring normal cells, and substantially reduces but does not completely abrogate alloreactivity. γ9δ2TCR-transduced αβT cells reduced colony formation of progenitor cells of primary acute myeloid leukemia blasts and inhibited leukemia growth in a humanized mouse model. Thereby, metabolites of a dysregulated mevalonate pathway are targeted and the additional application of widely used biphosphonates is crucial for in vivo efficacy most likely because of its modulating effect on cytokine secretion of γ9δ2TCR-transduced αβT cells. Expression of NKG2D ligands and F1-ATPase contributed to the activity of γ9δ2TCR-transduced αβT cells but were not mandatory. In summary, γ9δ2 TCRs are an attractive alternative to broadly redirect αβT cells against cancer cells with both an improved efficacy and safety profile compared with currently used αβTCRs.     

Clonal expansion of γδ-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis

 We report on an HTLV-I carrier showing clonal proliferation of γδ-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/μl with 89% lymphocytes. The proliferating γδ-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCRδ1, and HLA-DR but negative for CD4, CD8, and δTCS1. Clonally rearranged TCRγ-chain (Jγ) and TCRβ-chain (Cβ1) genes were detected by Southern blot analysis. Clonality of these proliferating γδ-T cells was confirmed by CDR3 size analysis for the TCRδ-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral DNA was detected by PCR analysis, but clonal integration of HTLV-I proviral DNA was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCRαβ+ type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation. Received: June 12, 1998 / Accepted: October 5, 1998     

Chlamydia muridarum respiratory tract infection induces the proliferation of γδT cells and the secretion of IFN-γ and IL-17

<正>Objective To investigate the proliferation,activation and cytokine production ofγδT cells during different periods of Chlamydia muridarum(Cm)respiratory tract infection.Methods C57BL/6 mice were inoculated intranasally with 3×103inclusion-forming units(IFU)of Cm strains to induce the murine model of chlamydial     

CD27+ γδT淋巴细胞与远端胃癌根治术后患者临床病理特征及预后的关系

目的 探究CD27⁺γδT淋巴细胞与远端胃癌根治术后患者的临床病理特征及预后的关系。方法 选择2019年3月至2020年3月在十堰市国药东风总医院接受根治性手术的102例远端胃癌患者,收集术后胃癌组织和癌旁组织标本,制备单细胞悬液。记录患者的临床病理资料,采用流式细胞术检测CD27⁺γδT细胞表达。术后对所有患者进行为期2年的随访,记录总生存期(OS)。分析胃癌组织中CD27⁺γδT淋巴细胞表达与患者临床病理特征的相关性。采用Kaplan-Meier法分析胃癌组织中CD27⁺γδT淋巴细胞表达与患者预后的关系。采用ROC曲线分析CD27⁺γδT淋巴细胞表达判断患者预后的效能。结果 远端胃癌根治术后患者的胃癌组织中CD27⁺γδT淋巴细胞的占比显著高于癌旁组织(P<0.05)。Ⅲ～Ⅳ期、高分化、有淋巴结转移患者的胃癌组织中CD27⁺γδT淋巴细胞占比分别高于Ⅰ～Ⅱ期、未分化及低/中分化、无淋巴结转移患者,组间差异均有统计学意义(P...     

Kinetics of pDCs, mDCs, γδT cells and regulatory T cells in association with graft versus host disease after hematopoietic stem cell transplantation

Introduction: Although the roles of each low‐frequency immunocompetent cells such as dendritic cells (DCs), γδT cells, and Treg cells in induction of acute or chronic graft versus host disease (GVHD) have been discussed in several reports, there are few papers dealing with an evaluation of these immunocompetent cells together and simultaneously in patients with hematopoietic stem cell transplantation (HSCT) and explored the kinetics of these cells in association with GVHD. Methods: In the present study, we assessed the number of plasmacytoid DCs (pDCs), myeloid DCs (mDCs), γδT cells and Treg cells serially in patients who received allogeneic HSCT and analyzed the relationship of these cells with acute or chronic GVHD (cGVHD) by using flow cytometry. Results: The percentages and numbers of pDCs, mDC1s and γδT cells were significantly lowered in the patients with acute GVHD (aGVHD) compared with those with no GVHD. On the contrary, the percentages and numbers of Treg cells were significantly elevated in the patients with aGVHD compared with those with no GVHD. As to the association with cGVHD, Treg cells were elevated in the patients with cGVHD, compared with those with no GVHD. Conclusion: The present study revealed an association of pDCs, mDCs, γδT cells and Treg cells with induction or treatment of GVHD.     

Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses

AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P 0.05 each), but enhanced the expression of IL-10 and Foxp3(P 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells.