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Psoriasis vulgaris is a recurrent inflammatory skin disease. A variety of factors, such as trauma and infection, can destroy the skin barrier function, thereby breaking the balance of immune homeostasis and tolerance, causing abnormalities in function and/or number of various immune-related cells in local skin, resulting in psoriasis-like skin changes such as abnormal proliferation of keratinocytes and excessive inflammatory reactions in skin lesions. Various immune cells in skin lesions can sense changes in the surrounding environment (autocrine or paracrine) through surface molecules, and then express and secrete a variety of inflammation-related factors; if maintenance mechanisms for immune homeostasis and tolerance become invalid, the positive feedback network of inflammation mediated by inflammation-related factors will be formed locally, leading to the occurrence of psoriasis vulgaris. This review summarizes research progress in the role of immune-related cells in skin lesions in the immunopathological mechanism of psoriasis vulgaris, especially innate immune cells such as γδT cells.
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Objective To investigate the cell origin of interleukin (IL)-22-secreting cell of mice infected with Trichinella spiralis (T.spiralis) at the early encapsulated stage.Methods Twelve Balb/c mice were divided into the infected group and the control group according to body weight by random number table.The infected mice were intragastrically administrated with 300 muscle larvae of T.spiralis,and the control mice were given the same amount of normal saline.The IL-22-secreting cell subsets in mouse splenic lymphocytes were detected by flow cytometry at the fourth week after infection.Results The proportion of IL-22-secreting cells in splenic lymphocytes of T.spiralis infected mice was increased when compared with control group [(0.88 ± 0.25)％ vs (0.28 ±0.17)％,t =-4.899,P ＜ 0.05].There was no significant difference between the proportion of CD3+IL-22+ cells and CD3-IL-22+ cells in the splenic lymphocytes of the infected group [(0.29 ± 0.17)％ vs (0.51 ± 0.17)％,t =-2.195,P ＞ 0.05],and the percentage of CD3-IL-22+ cells were similar between the infected group and the control group [(0.51 ± 0.17)％ vs (0.44 ± 0.22)％,t =-0.600,P ＞ 0.05].The proportion of CD3+IL-22+ cells in the infected group was significantly higher than that in the control group [(0.29 ± 0.17)％ vs (0.07 ± 0.06)％,t =-3.068,P ＜ 0.05],and the percentage of CD4+IL-22+ T cells and γδTCR+IL-22+ T cells were obviously increased in CD3+ lymphocytes [(1.28 ± 0.54)％ vs (0.16 ± 0.07)％,(0.33 ± 0.22)％ vs (0.02 ± 0.00)％,t =-4.997,-3.342,P ＜ 0.05].Conclusions The proportion of IL-22-secreting splenic lymphocytes is increased in mice infected with T.spiralis at the early encapsulated stage.The rise is caused by increased numbers of IL-22-secreting CD3 + lymphocytes,especially CD4+ T cells and γδT cells.
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Malaria is a kind of disease detrimental to human health and plasmodium is a critical pathogen in it. The immunity against foreign antigens including plasmodium could be divided into two categories, namely, adaptive immunity and innate im-munity. Innate immunity induces non-specific immune response, and is composed of monocyte,macrophage,γδT cell,DC,NK, and cytokines etc. Innate immunity cooperates with adaptive im-munity efficiently to protect against malaria. Meanwhile,autoph-agy is not only the cellular degrading process, but also gets in-volved in regulating immune system and defending against plas-modium infection. Therefore, elucidation of corresponding mechanism could provide proof for efficiently controlling and cu-ring malaria,developing related medicine and vaccine,and clin-ical treatment as well. This article reviews the constitution of in-nate immunity in malaria,related regulation mechanism and rel-evant therapeutic targets for it.
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Objective After the islet transplantation,observed blood glucose and survival time in the islet transplantation mice model to explore the effect of intestinal epithelial γδT cell in islet transplantation rejection.Methods Established the mice model of islet transplantation,divided into wild type mice group,γδ gene knockout mice group and γδ gene knockout γδT cell reinfusion mice group,observed blood glucose in 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 days after surgery and pathological conditions aft er two weeks of transplantation.Results After transplantation,the rising blood glucose of wild type mice group and γδ gene knockout γδT cell reinfusion mice group were significantly slower than that of γδ gene knockout mice group (P＜0.05),but there was no significant difference in between two groups (P＞0.05).The survival time of wild-type mice group was (27±2) days,and γδ gene knockout γδT cell reinfusion mice group was (24±1) days,they were significantly longer than (17±3) days of γδ gene knockout mice group (P＜ 0.05).Conclusion As a special kind of T cells,γδT intestinal epithelial cell plays an important role in the islet transplantation rejection.
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Objective:To investigate the distribution of γδT17,Th17 and Tc17 cells in the lung of mice severely infected by influenza A(H1N1)pdm09 virus and the relationship between these cells with lung immunopathalogical injury.Methods:Intranasal infection was used to establish mouse model of severe H1N1 infection.Flow cytometry assay was used to detect the proportion and number of γδT17 cells,Th17 cells and Tc17 cells in the lung.The concentrations of interleukin-17A(IL-17A),interleukin-1β(IL-1β)and interleukin-23(IL-23) in the bronchoalveolar lavage fluid and serum were assayed by enzyme-linked immunosorbent assay and Lu-minex assay.Results:①The model of mice severely infected by influenza A(H1N1)pdm09 virus was established successfully.②The ratio of γδT cells,but not CD4+T and CD8+T cells in total lymphocytes of the lung of infected mice significantly increased compared with uninfected control mice at the third day post infection(DPI)(P<0.01).③The proportion and number of γδT17 cells,Th17 cells and Tc17 cells in total γδT cells,Th cells and Tc cells in the lung of infected mice were significant higher than that in uninfected control mice at the first DPI,respectively.However,the absolute number of γδT17 cells was far more than Th17 and Tc17 cells(P<0.05);④The concentration of IL-17A in BALF increased significantly after infection(P<0.05),and the concentration of IL-17A in serum increased significantly at the third DPI(P<0.05).The concentrations of both IL-1β and IL-23 in BALF probably participating in the activation of γδT17 cells increased significantly after infection compared with uninfected control mice.Conclusion:The γδT17 cells could be activated and secreted IL-17A via γδTCR non-depended pathway and involved in inflammatory pathological injury of lung at the early stage of severe H1N1 infection.
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Objective:To study the immunotherapy effects of different doses of human peripheral blood γδT cells on human hepatoma cells (SMMC-7721) xenograft model.Methods: (1)The nude mouse model of liver cancer was established by inoculated BALB/c mouse subcutaneous with human hepatoma cell line (SMMC-7721).(2)The mononuclear cells in healthy human were extracted from peripheral blood,and specific amplification γδT cells in vitro.(3) The nude mouse model divided into 5 groups by random.The positive control group was 5-Fu,negative control group was normal saline(NS).The treatment group was injected different doses of γδT cells(1×105,5×105 and 25×105)by nude mice tail vein.The positive control group injected 5-Fu by enterocoelia,negative control group injected NS by tail veins.The inhibition effect of different dose γδT cells on tumor was observed,including weight,food intake and growth conditions,etc.and the changes of tumor volume (TV),relative tumor volume (RTV)and relative tumor appreciation rate[T/C(%)] were compared with positive control group and negative control group.Results: Different dose of γδT cells had different degree of inhibition on nude mouse xenograft growth.RTV compared with saline negative control group was statistically significant (P<0.05).Compared with the positive control group of 5-Fu,the TV growth was significantly lower than the 5-Fu,degree of inhibition was similar in RTV each dose group,and all slightly higher than the 5-Fu positive control group.The each dose group of T/C (%)was slightly lower than the relative tumor proliferation rate of the control group of 5-Fu,but had no significant difference.Conclusion: The γδT cells from peripheral blood had significant inhibitory effect on nude mice transplanted liver tumor and it may be used as a new treatment for liver cancer immunotherapy provide experimental data.
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Recently,an unconventional T cell population (collectively designated as Vδ2 -γδT cell ) has been characterized during the anti-cytomegalovirus immune response in all organ transplant recipients,neo-nates,and healthy individuals.These cytomegalovirus-induced Vδ2 -γδT cells undergo a dramatic and stable ex-pansion after cytomegalovirus infection,in a conventional adaptive way.Similarly,as cytomegalovirus-specific CD8 +αβT cells,they exhibit an effector/memory TEMRA phenotype and cytotoxic effect or functions.This paper reviews the researchs and reports about cytomegalovirus induced-Vδ2 -γδT cell,including its location,phe-notype,and activation,as well as its immunologic mechanism in cytomegalovirus infection,acute or chronic re-jection,and anti-cancer function.
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Objective:To study the role of γδ T cells and Vδ1 and Vδ2 T subsets played in patients with chronic hepatitis C.Methods:The percentage of peripheral bloodγδT cells and Vδ1 and Vδ2 T subsets cells was assessed by flow cytometry ( FACS) . Results:There were no significant differences in the percentage of circulating γδ T cells and Vδ1 and Vδ2 T subsets between HCV-infected patients and healthy controls ( HCs).However,The number of peripheral blood Vδ2 T cells from HCV-infected patients was positively correlated with serum alanine aminotransferase ( ALT) levels,but showed no correlation with serum HCV RNA.Peripheral Vδ2 T cells from HCV-infected patients were in activated status.The expression of CD107a was enhanced in Vδ2 T cells from HCV-infected patients compared to HCs.Conclusion:Vδ2 T cells were involved in liver injury in chronic HCV-infected patients.
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T cells are divided into two subsets,αβΤandγδT cells, according to the T-cell recep-tor ( TCR) expressed. γδT cells are a small minority of T cells and in contrast to αβΤ cells, they do not seem to require antigen processing and major-histocompatibility-complex ( MHC ) presentation of peptide epitopes. This group of T cells is usually much less common than αβT cells, but plays an important role in anti-infection, anti-tumor and immunoregulation. This review summarizes the production, development, dis-tribution, genetic characteristics, antigen recognition characteristics, biological and immunological functions of γδT cells as well as their unique roles and mechanisms in bacterial infectious diseases.
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Objective To investigate the cytotoxic activities of γδT cells against methotrexate (MTX)-resistant osteosarcoma (OS) cells.Methods The MTX-resistant U2OS cell line (U2OS/MTX) was established by in vitro exposing the parental cells to MTX at stepwise-increasing concentrations.Periph-eral blood mononuclear cells ( PBMCs) were isolated from healthy subjects and stimulated with zoledronate ( ZOL) in combination with IL-2 to induce the proliferation ofγδT cells.The cytotoxicity ofγδT cells against U2OS/MTX cells was analyzed by using a standard lactate dehydrogenase release assay (LDH).Flow cy-tometry analysis and ELISA were performed to detect the expression of CD69 and IFN-γby γδT cells, re-spectively.Results The γδT cells derived from healthy subjects showed cytotoxicity against the U2OS/MTX cells.Moreover, stronger cytotoxic activities of γδT cells were detected after pretreatment of U2OS/MTX cells with ZOL (1 μmol/L) for 24 hours (P<0.01).Stimulation with U2OS or U2OS/MTX cells in-creased the expression of CD69 onγδT cells and enhanced the secretion of IFN-γbyγδT cells (P<0.05). Increased expression of CD69 and enhanced secretion of IFN-γwere induced in γδT cells in response to stimulation with ZOL-pretreated U2OS/MTX cells (P<0.01).Conclusion TheγδT cells showed cytotox-icity against U2OS/MTX cells.Pretreatment of U2OS/MTX cells with ZOL could enhance the cytotoxic ac-tivity of γδT cells.
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Objective:To investigate the specific stimulation of the B cell epitope peptides of Mycobacterium tuberculosis antigen (Mtb-Ag) on human peripheral γδ T cell proliferation.Methods: We selected the sequences of B cell epitope peptide from Mtb-Ag that were reported in literature and T cell epitope peptide that recently identified in this laboratory to synthesize six peptides of B cell epitopes (BP1-BP6) and two peptides of γδ T cell epitopes (TP14,TP15).The 24-well culture plates were coated with these peptides.The PBMCs were isolated from peripheral blood of healthy individuals and stained with CFSE,followed cultured for 12 days in the IL-2 containing medium.Mtb heat resistant antigen ( Mtb-HAg ) group as positive control and IL-2 only group as negative control.The percentages and proliferation index of γδ T cells were determined by flow cytometry.Results: By using Wilcoxon signed rank test for paired comparison of negative control group,the percentages of γδ T cells in cultured PBMCs with BP2,BP4 and TP14, TP15 and Mtb-HAg increased significantly in 14 samples (P<0.05);and the proliferation index of γδT cell in cultured PBMCs with BP2,BP4,BP5,BP6 and TP14,TP15 increased significantly in 7 samples (P<0.05).Conclusion: Taken together,the B cell epitope peptides from Mtb Antigens are capable of stimulating the γδ T cell proliferation specifically in vitro.Although there was individual difference inγδT cell proliferative response to B cell epitope peptides,these results strongly suggest the B cell epitope peptides also can specifically trigger the TCR ofγδT cells.
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Objective To investigate the clinic characteristics of hepatosplenic γδT cell lymphoma (γδ HSTCL) and analyze the important role of morphology,immunology,cytogenetics and molecular(MICM) in the early diagnosis of γδHSTCL.Methods The clinical features of MICM of a rare case of childhood γδHSTCL had been analyzed,and the related literatures were reviewed.Results Bone marrow aspiration showed approximately 0.365 abnormal cells infiltrated.The immune phenotype analysis displayed 0.245 of the nuclear cells were abnormal ones,which possessed CD2/CD3/CD7/CD19/CD3s/cCD3 and TCRγδ expression.The immunohistochemical staining of spleen tissues showed clusters of differentiation (CD) 3/CD45 RO/CD8/Cytotoxic-granule associated protein (TIA-1)/leukocyte common antigen (LCA)/Granzyme B positive,CD4/CD20/T cell receptor (TCR) β/CD79 α/CD30/terminal deoxynucleotidy transferase (TdT) /CD10/ myeloperoxidase (MPO)/anaplasticlymphoma kinase (ALK) negative and 80.00％ of tumor cells displayed Ki-67 positive.The detection of spleen tissues by flow cytometry displayed that 72.26％ of the karyocytes were lymphocytes,with 88.90％ T lymphocytes.And 92.09％ of the T lymphocytes showed Ki-67/CD7dim,TCRγδ/CD2/CD8/CD34 positive,and TCRαβ/CD5/CD4/CD56 negative.And about 59.16％ of these karyocytes were abnormally matured T lymphocytes.The cytogenetic karyotype of bone marrow showed 46,XY.The detection of T cell receptor gene rearrangement showed TCRβ,TCRγ and TCRδ positive.The patient had been given prednisone of 60 mg/m2 when the diagnosis of γδHSTCL affirmed.But his parents discontinued chemotherapy for him and died.Conclusions MICM has shown a significant value in the diagnosis of γδHSTCL,a rare lymphoma in childhood.
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Objective:To investigate the effect of typeⅠIFN on the cytotoxic activity ofγδT cells from peripheral blood mono-nuclear cells ( PBMCs) of healthy donors and osteosarcoma patients stimulated by zoledronate ( Zol) and IL-2 against OS.Methods:PBMCs from healthy donors and osteosarcoma patients were stimulated with Zol+IL-2 or Zol+IL-2+typeⅠIFN,respectively.After 14 days of culture,ex vivo expandedγδT cells were assessed by flow cytometry.γδT cell cytotoxicity against target cells was analyzed using a standard lactate dehydrogenase release assay.IFN-γsecreted fromγδT cells was determined by ELISA kits.Results:γδT cells from PBMCs of healthy donors and patients with OS were selectively expanded by Zol+IL-2 or Zol+IL-2+typeⅠIFN in vitro,respectively, and showed cytotoxicity against OS.In addition,γδT cells pre-treated by TypeⅠIFN showed significantly higher cytotoxicity against OS cells.Conclusion:Type I IFN can enhance humanγδT cells’ cytotoxic activity against OS.
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γδT cells account for approximately 1％-10％ of T lymphocytes in peripheral blood,but they are more abundant in mucosal tissue.γδT cells can produce a diverse range of cytokines to exert cytotoxic effector function.In addition,γδT cells can act as antigen-presenting cell(APC) to enhance the activity of effector T cells and contribute to autoimmunity.Based on the recognized ligands and their common lack of major histocompatibility (MHC) restriction,γδT cells are considered as nontraditional T cells that link innate and adaptive immunity.Previous studies showed that γδT cells have dual function.They can help to strengthen an immune process,and they might also help to suppress immune response.Up to now,many researches have focused on how γδT cells to impact and regulate the experimental autoimmune uveitis by the interaction between γδT cells with αβT cells,interleukine-17 (IL-17),regulatory T cell (Treg),dendritic cell(DC) and toll-like receptor(TLR).In uveitis,a further understanding of the plasticity of γδT cells is required to specifically identify strategies for intentional modulation of their beneficial or detrimental regulatory activity.Here,the basic biological characteristics and the current knowledge on the regulation mechanism of γδT cells in uveitis disease were reviewed.
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Objective To investigate the in vitro effects of quercitrin on the proliferation and the cytotoxicity of human γδT cells.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects and cultured with isopentenyl pyrophosphate and IL -2 to induce human γδT cells.The hu-manγδT cells were cultured with quercitrin at various concentrations for 48 hours.CCK-8 kits were used to analyze the in vitro proliferation and cytotoxic activities of γδT cells.Flow cytometry was performed to meas-ure the expression of granzyme B and perforin in γδT cells.The expression of p-ERK, p-Akt and Bcl-2 at protein level were detected by Western blot .Results The percentage of human γδT cells in PBMCs was in-creased from (2.96±1.83)%to (88.94±2.36)%after 10 days of culture.The quercitrin at concentrations of 10 to 80 μg/ml could promote the growth of γδT cells and up-regulate the expression of granzyme B , per-forin, p-ERK, p-Akt and Bcl-2 in a dose dependent manner .The cytolytic activities of γδT cells against co-lonic carcinoma cells ( HCT116 ) were enhanced by quercitrin .Conclusion Quercitrin could promote the proliferation of γδT cells and enhance the expression of granzyme B and perforin at certain concentrations in vitro.ERK1/2 and Akt signal transduction systems might be involved in the process .
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Objective To investigate the effect of DHA on proliferation and killing activity of γδT cells against SW1990 cells in vitro.Methods γδT cells were generated in vitro by stimulating peripheral blood mononuclear cells of healthy donors in RPMI 1640 completed medium containing IPP and IL-2 for 8 d,and then co-cultured with different concentrations of DHA for 48 h.Proliferation rates of γδT cells for each group were detected by MTT method.The perforin,granzyme B and CD107a expression in γδT cells were verified by flow cytometer.The cytotoxic activity of γδT cells against SW1990 cells were analyzed by CCK-8 kit.Results The purity of γδT cells in each group reached 75.46％ ±5.32％ after 8 d of culture.Compared with the control group,the proliferative capability of γδT cells were enhanced significantly after treated with 50-100 μmol/ml DHA for 48 h,moreover,cytotoxicity against SW1990 cells and perforin,granzyme B and CD107a expression of the γδT cells treated with DHA were higher than the control group.Conclusion DHA could enhance the antitumor activity of γδT cells,which may be associated with the upregulation of perforin and granzyme B expression in γδT cells.
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Objective To study the effect of interleukin 2(IL-2)of clinical dose range,on the proliferation of human peripheral blood T cells,with special emphasis on the number and functional phenotype of γδT cells.Methods Human peripheral blood mononuelear cells(PBMCs)were isolated by density gradient centrifugation and cultured for 2 weeks at different IL-2 concentrations.Ratio and phenotype of different T cell subpopulations before and after in vitro expansion were explored by immunofluorescence staining.Cell number was estimated by trypan blue staining and cell counting.Results Within the four functional phenotypes of Vδ1 as well as Vδ2 γδT cells,CD27~+cells(including CD27~+CD45RA~+and CD27~+CD45RA~-subsets)expressed lymphoid tissue homing receptor CCR7,whereas CD27~-cells(including CD27~-CD45RA~+and CD27~-CD45RA~-subsets)had the peripheral tissue homing potential.All the studied γδT functional subsets showed the expression of activity related receptors,and the ability of a rapid production of various amount of cytotoxicity related effectors following mitogen stimulation.Although IL-2 at high concentration suppressed the proliferation of CD4 T cells,it may promote the proliferation of γδT cells.The proliferated γδT cells were mainly CD27~-CD45RA~-effector cells.Conclusion IL-2 of the clinical dose range may promote proliferation of human peripheral blood γδT cells,which might have important biological significance in IL-2 based anti-tumor therapy.