A simple and rapid method for propagation and purification of the peripheral blood gammadeltaT cells.
Wang Ke-Qiang,Hou Yan-Qiang,Li Yan
Zhongguo shi yan xue ye xue za zhi
The purpose of this study was to set up an approach for expansion of the peripheral blood gammadeltaT cells from normal subjects in order to explore the characteristics of gammadeltaT cells. Peripheral blood mononuclear cells (PBMNC) were separated from 5 - 10 ml peripheral blood and stimulated by the low molecular peptide derived from Mycobacterium tuberculosis (MTb-Ag), and expanded in rIL-2-containing medium. The relative amount of gammadeltaT cells were measured by anti TCR gammadelta-PE staining and flow cytometry. The Cytotoxicity were detected by gammadeltaT assay. The results showed that after stimulation and expansion for 10 days, gammadeltaT cells increased to 69.2% of the total PBMNC and demonstrated significant cytotoxicity against K562 cells. In conclusion, this is a simple, rapid and specific method for expansion of peripheral blood gammadeltaT cells in vitro.
[Proportion and characteristics of γδT cells in different tissues and organs of C57BL/6 mice].
Huang Jun,Luo Xueping,Chen Dianhui,Fang Huilong,Xie Hongyan
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology
OBJECTIVE:To compare the percentages of γδT cells in the lymphocytes and CD3⁺; T cells isolated from the livers, lungs, spleen and mesenteric lymph nodes of C57BL/6 mice and the phonotype and function of γδT cells in different tissues or organs. METHODS:Lymphocytes were isolated from livers, lungs, spleen and mesenteric lymph nodes of normal C57BL/6 mice, respectively. Then, percentages of γδT cells in lymphocytes and CD3⁺; T cells, and phenotypic characteristics of γδT cells were examined by flow cytometry. Moreover, IFN-γ, IL-4, IL-9 and IL-17 secreted by γδT cells were detected by means of intracellular cytokine staining after stimulation with PMA plus ionomycin. RESULTS:The percentage of γδT in lymphocyte cells of the livers was significantly higher than that of the lungs, spleen and mesenteric lymph nodes (P<0.05), and the percentage in CD3⁺; T cells of the mesenteric lymph nodes was the lowest (P<0.05). CD4⁻; CD8⁻; γδT cells were the main subpopulation in these tissues and organs and there was also a small proportion of CD8⁺; γδT cells. The proportion of CD4⁺; γδT cells in the mesenteric lymph nodes was significantly higher than that in the others (P<0.05), and a group of CD4⁺; CD8⁺; γδT cells existed obviously. The percentage of IL-17⁺; cells in γδT cells was significantly higher than IFN-γ⁺; and IL-4⁺; cells, and almost no IL-9 γδT cells were found. The ability of secreting cytokines of γδT cells in the lungs was the strongest and the percentage of IL-17⁺; γδT was (26.6 ± 12.1) %. In addition, the proportion of IFN-γ⁺⁻; γδT cells in the livers and lungs were (1.36 ± 0.37)% and (1.6 ± 0.7)%, respectively. CONCLUSION:The proportion, phenotype and function of γδT cells had significant difference in the livers, lungs, spleen, mesenteric lymph nodes of C57BL/6 mice.
Expression of PD1 and BTLA on the CD8 T Cell and γδT Cell Subsets in Peripheral Blood of Non-Small Cell Lung Cancer Patients.
Bao Yi,Mo Juan-Fen,Wu Jia-Yuan,Cao Chen-Xi
Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih
To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8 T cells and γδ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. The frequency of PD1 on the surfaces of CD8 T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8 T cells, rather than on γδ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1 BTLAγδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1γδ and BTLAγδ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8 T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8 T cells and γδ T cells, immune escape and tumor invasion.
10.24920/003498
[Establishment of the culture system of γδ T cells and the anti-tumor effect].
Xie L,Chen W,Wang L,Cheng M,Hu S L,Shen G
Zhonghua zhong liu za zhi [Chinese journal of oncology]
To establish the culture technique for culturing γδ T cells and evaluate the basic characteristics, security and anti-tumor effect of the cultured γδ T cells. Phytohemagglutinin, zoledronic acid, interleukin-2 and interleukin -7 were used to induce the abundant expansion of peripheral blood mononuclear cells . Flow cytometry assay, killing assay and mouse model of human lung cancer were also adopted to assess the characteristics and the anti-tumor effect of cultured γδ T cells. Additionally, the contamination of exogenous agents and the acute toxicity of γδ T cells were determined. After culturing 14-16 days the total number of γδ T cells was more than 1.0×10(10). Among these γδ T cells, CD3(+) γδ TCR(+) cells accounted for more than 90%. None of contaminations of bacteria, fungi, mycoplasma and virus were observed. At effect target ratio (E/T ratio) of 50/1, killing efficiency of γδ T cells cultured to SK-MES-1, Ho8910, A549 and K562 reached more than 65%. experiments showed that the tumor volume of γδ T-treated mice was (828.99±61.05) mm(3,) significantly lower than (1 723.51±84.30) mm(3) of the control mice (<0.05). Meanwhile, no acute toxicity effect was observed in γδ T cells treated mice. The number, purity and activity of γδT cells cultured in our institute can reach the requirement of clinical application, and the γδT cells also display strong cytotoxic activity against tumor cells such as lung cancer, ovarian cancer and leukemia.
10.3760/cma.j.issn.0253-3766.2018.04.002
Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells.
Coughlin Beth,Schnabolk Gloriane,Joseph Kusumam,Raikwar Himanshu,Kunchithapautham Kannan,Johnson Krista,Moore Kristi,Wang Yi,Rohrer Bärbel
Scientific reports
Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment.
10.1038/srep23794
The features of circulating and tumor-infiltrating γδ T cells in melanoma patients display critical perturbations with prognostic impact on clinical outcome.
Girard Pauline,Charles Julie,Cluzel Camille,Degeorges Emmanuelle,Manches Olivier,Plumas Joel,De Fraipont Florence,Leccia Marie-Therese,Mouret Stephane,Chaperot Laurence,Aspord Caroline
Oncoimmunology
γδT cells hold a pivotal role in tumor immunosurveillance through their prompt activation and cytokine secretion, their ability to kill tumor cells in an Human Leukocyte Antigen (HLA)-unrestricted manner, and their combination of features of both innate and adaptive immunity. These unique properties and functional plasticity render them very attractive both as targets and vectors for cancer immunotherapy. Yet, these potent and fascinating antitumor effectors have not been extensively explored in melanoma. We provided here a detailed investigation of the phenotypic and functional properties of circulating and tumor-infiltrating γδT cells in melanoma patients, and their impact on clinical evolution. High proportions of circulating- and tumor-infiltrating γδT and δ2+ subset were associated with better clinical outcome. We reported however that circulating and tumor-infiltrating γδT cells from melanoma patients displayed an altered expression of NCR, KIR, and immune checkpoints, and identified NKp44, PD1, 41BB/41BBL, TIM3, and LAG3 as crucial checkpoints allowing immune escape and tumor progression. Notably, melanoma drastically impaired the ability of γδT cells to exhibit activation molecules, secrete cytokines, and display cytotoxicity toward melanoma in response to stimulation with phosphoantigens. It drove them toward regulatory and Th17 profiles associated with poor clinical outcomes. Our study highlights that melanoma hijacked γδT cells to escape from immune control, and revealed that circulating and tumor-infiltrating γδT cell features are promising potential biomarkers of clinical evolution. Such understanding of the physiopathology of γδT cells may help designing new therapeutic approaches exploiting the antitumor potential of γδT cells while counteracting their skewing by tumors to improve patient outcomes.
10.1080/2162402X.2019.1601483
Tandem-epitope peptide: a novel stimulator for gammadeltaT cells in tumor immunotherapy.
He Xiaojuan,Chen Hui,Wu Di,Cui Lianxian,He Wei
Cancer letters
T cells bearing the gammadeltaTCR have become the new candidate effectors in tumor immunotherapy because of their potent cytotoxicity toward various tumor cells. However, a crucial issue in using gammadeltaT cells as effectors is how to effectively expand tumor-reactive gammadeltaT cells and enhance their functions. In previously studies, we used synthesized CDR3-peptide derived from ovarian epithelial carcinoma (OEC) infiltrating gammadeltaT cells (gammadeltaTILs) as specific probe to screen a phage display peptide library and identified seven putative epitopes named EP1-EP7. All seven putative epitopes could not only bind to gammadeltaT cells, but also activate them in vitro. To enhance the activating capability of these identified gammadeltaT cell ligands, we have constructed four types of GST epitope fusion proteins containing single epitope or tandem epitopes. These GST epitope fusion proteins could not only promote the secretion of cytokines, but also enhance the proliferation and cytotoxicity of gammadeltaT cells in vitro. Significant difference between GST tandem-epitope groups and GST single-epitope group in their activating capability was observed (P<0.05). Furthermore, GST epitope fusion proteins could suppress the growth of tumor and prolong the survival of BALB/c nude mice inoculated with human OEC cell line (P<0.05). In conclusion, these results provide a novel approach for tumor immunotherapy based on gammadeltaT cells.
10.1016/j.canlet.2009.06.024
Identification of gammadeltaT lymphocytes in human periapical lesions.
McCutcheon J A,Yee H,Hayashi R,Licari B,Lombardo D,Rosenberg P A,Phelan J
Oral microbiology and immunology
Endodontic (root canal) therapy is required when the pulp of a tooth becomes necrotic due to a bacterial infection or trauma. A proportion of patients who receive endodontic therapy subsequently have periapical (around the tooth root) lesions detected by radiolucency. Currently, there are no means to identify susceptible patients. Although tissue from periapical lesions has been described as inflammatory, inflammatory cell types and their functions have been poorly characterized. For example, T lymphocytes were identified using pan specific anti-CD3 mAb, which recognizes both alphabeta and gammadeltaT cells. Using the current model of gammadeltaT cells as immunoregulatory cells; gammadeltaT cells can mediate protective or destructive milieus. We postulated that patients who have a periapical lesion, as identified by radiographic bone loss, mount a gammadeltaT cell response. We collected specimens removed by surgery from both periapical lesions and other oral tissues, generated total RNA and performed reverse-transcriptase polymerase chain reaction to identify rearranged delta genes. Results were confirmed with semi-nested polymerase chain reaction. In addition, we demonstrate that these lesions contain a population of CD3+ cells that are alphabetaT cell receptor negative, implying that these cells are gammadeltaT cells. Here we show that 36/37 of periapical lesions and only 2/11 of other lesions contain gammadeltaT cells (P<0.0001). Vdelta2+ T cells were the most common subtype identified (30/36) in these samples. This is the first report in the literature of the presence of gammadeltaT cells in human periapical lesions.
10.1046/j.0902-0055.2004.00124.x
Flow Cytometric Pattern of TCRVδ Subtype Expression Rapidly Identifies γδT Cell Lymphoma.
Chen Xiao,Zhao Sishu,Liu Lu,Qiao Chun,Wang Yan,Fan Lei,Jin Huimin,Wu Yujie
Frontiers in oncology
γδT cell lymphoma (γδ TCL) is a class of hematopoietic malignancy that expresses the γδ T cell receptor (TCR) with a low incidence. Determining the clonal proliferation of γδT cells is important for the diagnosis of such malignancies. Few studies have used flow cytometry to detect VδTCR and its subtypes (Vδ1 and Vδ2) at the protein level, although it is a practical method for determining the neoplastic γδT cells. A TCRVδ-based 10-color protocol was designed for the detection of malignant proliferation of γδT subtype cells by multiparameter flow cytometry, and the diagnostic results were compared with the gene rearrangement results. All 19 cases of γδ TCL were positive for cluster of differentiation 3 (CD3) and TCR γδ and presented with abnormal distribution patterns of Vδ1 and Vδ2, of which 16 of the 19 cases showed a restricted Vδ1 staining pattern and the remaining three cases lacked the expression of either Vδ1 or Vδ2. Among the 10 normal controls and 11 patients with reactively higher CD4 and CD8 double-negative ratio, the percentage of Vδ2 positive events (range: 16.4-99.0%) was significantly higher than that of Vδ1 (range: 0-50.5%; < 0.0001), and all cases had a normal Vδ distribution pattern. To detect clonality, there was no difference in the detection rate between the TCRVδ analysis and the gene scanning techniques ( = 1.000) with a high degree of coincidence (Kappa = 0.850, < 0.001). The heteroduplex analysis was less sensitive than the other methods but was more specific (100%) than the gene scanning techniques, and the TCRVδ subtype analysis had the highest sensitivity, specificity, positive predictive value, and negative predictive value. Compared with molecular methods, immunophenotyping is able to distinguish the T cell lineage. The γδT panel, based on the TCRVδ antibody by flow cytometry, could be advantageous for the rapid identification of suspected γδTCL.
10.3389/fonc.2020.00844
C5a/C5aR1 mediates IMQ-induced psoriasiform skin inflammation by promoting IL-17A production from γδ-T cells.
Zheng Quan-You,Xu Feng,Yang Yi,Sun Dao-Dong,Zhong Yu,Wu Shun,Li Gui-Qing,Gao Wei-Wu,Wang Tao,Xu Gui-Lian,Liang Shen-Ju
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Psoriasis is a chronic relapsing inflammatory skin disease, affecting up to 3% of the global population. Accumulating evidence suggests that the complement system is involved in its pathogenesis. Our previous study revealed that the C5a/C5aR1 pathway is crucial for disease development. However, the underlying mechanisms remain largely unknown. To explore potential mechanisms, psoriatic skin lesions and histological changes were assessed following imiquimod (IMQ) cream treatment. Inflammatory cytokine expression was tested by real-time RT-PCR. Immunohistochemistry and flow cytometry were used to identify inflammatory cell infiltration and interleukin (IL-17A) IL-17A expression. A C5aR1 antagonist (C5aR1a) and PI3K inhibitor (wortmannin) were used for blocking experiments (both in vivo and in vitro) to explore the mechanism. C5a/C5aR1-pathway inhibition significantly attenuated psoriasis-like skin lesions with decreased epidermal hyperplasia, downregulated type 17-related inflammatory gene expression, and reduced IL-17A-producing γδ-T cell responses. Mechanistically, C5a/C5aR1 promoted the latter phenotype via PI3K-Akt signaling. Consistently, C5aR1 deficiency clearly ameliorated IMQ-induced chronic psoriasiform dermatitis, with a significant decrease in IL-17A expression. Finally, blocking C5aR1 signaling further decreased psoriasiform skin inflammation in IL-17-deficient mice. Results suggest that C5a/C5aR1 mediates experimental psoriasis and skin inflammation by upregulating IL-17A expression from γδ-T cells. Blocking C5a/C5aR1/IL-17A axis is expected to be a promising strategy for psoriasis treatment.
10.1096/fj.202000384R
γδ T Cells Modulate Myeloid Cell Recruitment but Not Pain During Peripheral Inflammation.
Frontiers in immunology
Circulating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are γδT cells, which serve important roles in infection, disease, and wound healing. Using a mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of peripheral inflammatory pain were used: intraplantar injection of formalin (spontaneous inflammatory pain), incisional wound (acute inflammatory pain), and intraplantar injection of complete Freund's adjuvant (chronic inflammatory pain). Our results show that absence of γδT cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. Myeloid cell recruitment did show differential changes between models of acute and chronic inflammatory pain. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that γδT cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.
10.3389/fimmu.2019.00473
IL-21 is required for the maintenance and pathogenesis of murine Vγ4 IL-17-producing γδT cells.
Frontiers in immunology
Murine IL-17-producing γδT (γδT17) cells are divided into two subsets: natural γδT17 (nγδT17) cells, whose development is restricted to the fetal thymus, and inducible γδT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from immature γδT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vγ4. Although IL-23 is known to be involved in developing γδT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of γδT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of nγδT17 cells but is required for the peripheral maintenance of Vγ4nγδT17 cells. Upon stimulation with γδTCR, IL-1 plus IL-21 induces the proliferation of Vγ4nγδT17 cells via STAT3 as effectively as IL-1 plus IL-23. Using bone marrow chimeric mice, we demonstrated that immature γδT17 cells are produced in the adult mice from donor adult bone marrow cells and that IL-21 is dispensable for their development. Instead, IL-21 is required to expand newly induced Vγ4γδT17 cells in the periphery upon immunization. Finally, using adoptive transfer experiments of γδT17 cells, we found that IL-21 receptors on γδT17 cells are involved in maintaining Vγ4γδT17 cells, subsequent infiltration of Th17 cells into the spinal cord, and exacerbation of experimental autoimmune encephalomyelitis. Collectively, IL-21 plays a vital role in the maintenance and pathogenesis of Vγ4γδT17 cells.
10.3389/fimmu.2023.1211620
γδT-cell function in sepsis is modulated by C5a receptor signalling.
Han Gencheng,Geng Shaoxia,Li Yurong,Chen Guojiang,Wang Renxi,Li Xinying,Ma Yuanfang,Shen Beifen,Li Yan
Immunology
We previously showed that γδT cells are involved in the pathogenesis of sepsis, but, the underlying mechanisms remained unclear. The present study demonstrates, for the first time, that γδT cells express the complement C5a receptor (C5aR, CD88) and that CD88 expression in γδT cells was up-regulated in mice following sepsis both at protein and mRNA levels. Complement C5a itself contributed to the regulation of C5aR expression on γδT cells, as (i) neutralization of C5a in vivo prevented the expression of C5aR on γδT cells in septic mice and (ii) incubation of mouse spleen cells or purified γδT cells with recombinant C5a in vitro increased CD88 expression by γδT cells at both protein and mRNA levels. C5a receptor on γδT cells also mediates increased interleukin-17 (IL-17) expression as incubation of mouse spleen cells or purified γδT cells with recombinant C5a promotes the IL-17 expression by γδT cells. Ligation of the C5aR on γδT cells activated the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway, which enhances CD88 expression and promotes IL-17 secretion. These results demonstrate that C5a acts directly on the C5aR expressed on γδT cells, resulting in cell activation, and subsequently enhances their capacity for IL-17 production. The up-regulation of the PI3K/Akt pathway following C5a stimulation contributes to up-regulation of γδT-cell function.
10.1111/j.1365-2567.2011.03445.x
Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression.
Cuthbert Richard James,Watad Abdulla,Fragkakis Evangelos M,Dunsmuir Robert,Loughenbury Peter,Khan Almas,Millner Peter A,Davison Adam,Marzo-Ortega Helena,Newton Darren,Bridgewood Charlie,McGonagle Dennis G
Annals of the rheumatic diseases
OBJECTIVES:Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated γδT-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. METHODS:Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal γδT-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from γδT-cell subsets and analysed by qPCR. Entheseal γδT-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. RESULTS:Entheseal γδT-cells were confirmed immunohistochemically with Vδ1 and Vδ2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal Vδ2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the Vδ1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both Vδ1 and Vδ2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the Vδ1 subset following IL-23 stimulation. CONCLUSION:Spinal entheseal Vδ1 and Vδ2 subsets are tissue resident cells with inducible IL-17A production with evidence that the Vδ1 subset does so independently of IL-23R expression.
10.1136/annrheumdis-2019-215210
Non-V delta 2 gamma delta T lymphocytes as effectors of cancer immunotherapy.
Oncoimmunology
Gamma delta T cells (γδT) are potent mediators of antitumor cytotoxicity and have shown promising efficacy in early phase clinical trials. Most is known about the tumoricidal properties of cells bearing the Vδ2 T cell receptor chain, but recent studies have demonstrated that cells with the Vδ1 chain and those with neither Vδ1 nor Vδ2 chains have properties which may make them more attractive anticancer effectors in adoptive immunotherapy.
10.4161/2162402X.2014.973808
IL-17A-Producing γδT Cells Inhibit the Formation of Malignant Pleural Effusions.
Wei Xiao-Shan,Pei Xue-Bin,Liu Ya-Lan,Wu Xiu-Zhi,Shi Huan-Zhong,Zhou Qiong
American journal of respiratory cell and molecular biology
γδT cells are an important source of IL-17A and play an anti- or protumor role depending on the surrounding microenvironment. The precise role of γδT cells in the development of malignant pleural effusions (MPE) remains unknown. Using flow cytometry, we analyzed the distribution and differentiation of γδT cells in wild-type (WT) and mice. We carefully elucidated the influence of γδT cells on the formation of MPE by depleting γδT cells from WT, , and mice. The distribution of γδT17 cells in human MPE and peripheral blood was also determined. Our data showed that both γδT cells and IL-17A-producing γδT (γδT17) cells accumulated in murine MPE, and IL-10 deficiency enhanced their accumulation. γδT cells were the main source of IL-17A in MPE for both WT and mice. IL-10 inhibited the chemotactic response of γδT cells to MPE and the proliferation of these cells. IL-10 suppressed γδT cell secretion of IL-17A via RORγt. The ablation of γδT cells accelerated MPE accumulation in both WT and mice, but it did not influence MPE accumulation in mice. Patients with higher frequencies of γδT17 cells had significantly longer survival times than patients with lower frequencies of γδT17 cells. Taken together, our data demonstrate that γδT17 cells play an inhibitory role in the progression of MPE, and the accumulation of γδT17 cells in MPE is suppressed by IL-10.
10.1165/rcmb.2018-0201OC