Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination. Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity. It was recently shown that MAIT cells are present in the oral mucosal tissue, but the involvement of MAIT cells in AP is unknown. Here, comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33, Vα7.2-Jα20, Vα7.2-Jα12, Cα and tumour necrosis factor (TNF), interferon (IFN)-γ and interleukin (IL)-17A transcripts, resembling a MAIT cell signature. Moreover, in AP tissues the MR1-restricted MAIT cells positive for MR1-5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4 subset. Unlike gingival tissues, the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature. When merged in an integrated view, the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33, Cα, and IL-17A transcript expressions in AP, implying that MAIT cells could play a role in the local defence at the oral tissue barrier. In conclusion, we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place. These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.
Adult ; Aged ; Female ; Humans ; Immunity, Mucosal ; immunology ; Male ; Microbiota ; Middle Aged ; Mucosal-Associated Invariant T Cells ; Natural Killer T-Cells ; immunology ; Periapical Periodontitis ; microbiology ; surgery

OBJECTIVE: To study the correlation of IL-37 with T lymphocytes subsets and NK cells in ITP patients, and to explore its possible mechanisms involved in the pathogenesis of ITP. METHODS: Forty-five patients with newly diagnosed ITP(newly diagnosed group), 32 patients of complete remission (remission group) and 22 healthy persons(control group) were selected. The serum level of IL-37 in 3 groups was determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression of IL-37, IL-17 and IL-18 in peripheral blood mononuclear cells（PBMNC） in 3 groups was measured by real-time fluorescence quantitative polymerase chain reaction (PCR). The number of IL-18RαCD4 T cells and Tim-3NK cells in the peripheral blood in 3 groups was detected by flow cytometry (FCM). RESULTS: The serum level of IL-37 in the peripheral blood of ITP patients in the newly diagnosed group was significantly higher than that in the control group and the remission group(P＜0.01) . The expression level of IL-37 in PBMNC of the ITP patients in newly diagnosed group was higher than that in the control group and the remission group(P＜0. 05). The expression level of IL-17 and IL-18 in PBMNC of the ITP patients in newly diagnosed group was higher than that in the control group and the remission group(P＜0. 01); the expression of IL-18Rα in CD4 T cells in newly diagnosed group was significantly higher than that in both the control and the remission group(P＜0.01).The expression of Tim-3 in NK cells in ITP patients was significantly lower than that in the control group (P＜0. 01). In ITP patients, the serum IL-37 level and IL-18RαCD4T cells ratio both negatively correlated with Plt count (r=-0.58, r=-0.48) moreo-ver the serum IL-37 level also negatively correlated with amount of CD4 T cells and NK cells (r=-0.29, r=-0.28), but positively correlated with amount of CD8 T cells (r=0.329). CONCLUSION The IL-37 and its receptors may play an immunoregulatory role in CD4 T cells and NK cells, the IL-37 may be a therapeutic target for ITP patients.
CD8-Positive T-Lymphocytes ; Flow Cytometry ; Humans ; Interleukin-1 ; immunology ; Killer Cells, Natural ; Leukocytes, Mononuclear ; Purpura, Thrombocytopenic, Idiopathic ; T-Lymphocyte Subsets

The study aimed to explore the in vivo immunoregulatory function of Grifola frondosa polysaccharide( GFP) on animal disease models. Databases of PubMed,Embase,Web of Scinece,CNKI,CBM and Wan Fang Data were searched from the date of their establishment to February 2018. Two reviewers independently screened included studies and evaluated their quality by using SYRCLE's risk of bias tool. R software was used to analyze the data. Finally,20 animal experiment studies were included. According to Metaanalysis. For cellular immunity,GFP could effectively enhance the proliferation of effect or T cells,natural killer cells and macrophages in mice. The percentage of CD4+T cells( MD = 1. 89,95% CI [0. 94,2. 83],P < 0. 000 1),CD8+T cells( MD = 8. 46,95% CI[5. 93,11. 00],P<0. 000 1),NK cells( MD= 2. 67,95% CI [0. 23,5. 11],P= 0. 03),and macrophages( MD= 14. 09,95% CI[0. 84,27. 34],P= 0. 04) were all higher than those in control group. For humoral immunity,GFP could increase the secretion of TNF-α and INF-γ． The secretion of TNF-α( SMD = 15. 92,95% CI [9. 07,22. 76],P<0. 000 1) and INF-γ( SMD = 5. 34,95% CI[3. 42,7. 26],P<0. 000 1) were all higher than those in control group. In conclusion,GFP could regulate immunologic function by enhancing the proliferation activity of immune cells( CD4+T cells,CD8+T cells,NK cells and macrophages) and the secretion of immune factors( TNF-α and INF-γ) ． However,it is necessary to further standardize the selection of specific surface markers of immune cells and the administration of GFP,in order to reduce the heterogeneity among the studies. At the same time,more attention shall be paid to experimental design,implementation and full report,especially to the establishment and implementation of animal experimental registration system,so as to improve the transparency and quality of the whole process of animal experimental research,enhance the value of basic research ultimately,and provide a reliable theoretical basis for the transformation of basic research into clinical research.
Animals ; Cytokines/immunology* ; Disease Models, Animal ; Grifola/chemistry* ; Immune System ; Killer Cells, Natural/immunology* ; Macrophages/immunology* ; Mice ; Polysaccharides/pharmacology* ; T-Lymphocytes/immunology*

With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.
China ; Dendritic Cells/immunology* ; Humans ; Immunity, Cellular ; Immunotherapy/methods* ; Killer Cells, Natural/immunology* ; Neoplasms/therapy* ; Patient Selection/ethics* ; T-Lymphocytes/immunology*

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.
Animals ; Autoimmune Diseases ; immunology ; Humans ; Liver ; pathology ; Liver Diseases ; immunology ; Natural Killer T-Cells ; immunology

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.
Animals ; HIV Infections ; immunology ; therapy ; HIV-1 ; immunology ; Humans ; Immunity, Cellular ; Immunological Synapses ; Immunotherapy ; Killer Cells, Natural ; transplantation ; Neoplasms ; immunology ; therapy ; Receptors, Antigen, T-Cell ; genetics ; immunology ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes ; immunology ; transplantation

Research on innate lymphoid cells (ILC) has recently been a fast paced topic of immunological research. As ILCs are able to produce signature Th cytokine, ILCs have garnered considerable attention and have been described to represent the innate counterpart of the CD4 T helper (Th) cells. The development and function of ILCs are precisely regulated by a network of crucial transcription factors, which are also involved in the development or differentiation of conventional natural killer (cNK) cells and T cells. In this review, we will summarize the key transcriptional regulators and their functions through each phases of ILC development. With the phase of ILC lineage commitment, we will focus in particular on the roles of the transcription regulators Id2 and GATA-3, which in collaboration with other transcriptional factors, are critically involved in the generation of ILC fate determined progenitors. Once an ILC lineage has been established, several other transcription factors are required for the specification and functional regulation of distinct mature ILC subsets. Thus, a comprehensive understanding of the interactions and regulatory mechanisms mediated by these transcription factors will help us to further understand how ILCs exert their helper-like functions and bridge the innate and adaptive immunity.
Animals ; GATA3 Transcription Factor ; immunology ; Humans ; Immunity, Innate ; physiology ; Inhibitor of Differentiation Protein 2 ; immunology ; Killer Cells, Natural ; immunology ; T-Lymphocytes, Helper-Inducer ; immunology

OBJECTIVETo study the changes and clinical significance of CD4CD25CD127regulatory T cells (Treg) and CD3CD16CD56natural killer T cells (NKT) in peripheral blood of children with Wilms tumor.

METHODSTwenty-one children with Wilms tumor were enrolled as the case group, and twenty-one healthy children for physical examinations were enrolled as the control group. Flow cytometry was used to detect the levels of CD4CD25CD127T cells and CD3CD16CD56T cells in peripheral blood of two groups.

RESULTSThe level of Treg cells in peripheral blood of the case group was significantly lower than in the control group (p<0.05). The level of NKT cells in peripheral blood of the case group was significantly higher than in the control group (p<0.05).

CONCLUSIONSTreg cells and NKT cells play important roles in the occurrence and development of Wilms tumor. Treg cells and NKT cells may be useful indexes for evaluating immunological function in children with Wilms tumor.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Kidney Neoplasms ; immunology ; Male ; Natural Killer T-Cells ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Wilms Tumor ; immunology

BACKGROUNDLymphocyte subsets play important roles in rejection in liver transplant recipients, and the effect of splenic function on these roles remains unknown. The aim of this study was to explore the feasibility to adjust immunosuppressive agents based on splenic function status through detecting the lymphocyte subsets in liver transplantBeijing recipients.

METHODSThe lymphocyte subsets of 49 liver transplant recipients were assessed in the 309th Hospital of Chinese People's Liberation Army between June 2014 and August 2015. The patients were divided into splenectomy group (n = 9), normal splenic function group (n = 24), and hypersplenism group (n = 16). The percentages and counts of CD4+ T, CD8+ T, natural killer (NK) cell, B-cell, regulatory B-cell (Breg), and regulatory T-cell (Treg) were detected by flow cytometer. In addition, the immunosuppressive agents, histories of rejection and infection, and postoperative time of the patients were compared among the three groups.

RESULTSThere was no significant difference of clinical characteristics among the three groups. The percentage of CD19+CD24+CD38+ Breg was significantly higher in hypersplenism group than normal splenic function group and splenectomy group (3.29 ± 0.97% vs. 2.12 ± 1.08% and 1.90 ± 0.99%, P = 0.001). The same result was found in CD4+CD25+FoxP3+ Treg percentage (0.97 ± 0.39% vs. 0.54 ± 0.31% and 0.56 ± 0.28%, P = 0.001). The counts of CD8+ T-cell, CD4+ T-cell, and NK cell were significantly lower in hypersplenism group than normal splenic function group (254.25 ± 149.08 vs. 476.96 ± 225.52, P= 0.002; 301.69 ± 154.39 vs. 532.50 ± 194.42, P= 0.000; and 88.56 ± 63.15 vs. 188.33 ± 134.51, P = 0.048). Moreover, the counts of CD4+ T-cell and NK cell were significantly lower in hypersplenism group than splenectomy group (301.69 ± 154.39 vs. 491.89 ± 132.31, P= 0.033; and 88.56 ± 63.15 vs. 226.00 ± 168.85, P = 0.032).

CONCLUSIONSplenic function status might affect the immunity of liver transplant recipients, that should be considered when we make immunosuppressive protocols.

CD4-Positive T-Lymphocytes ; drug effects ; immunology ; Female ; Humans ; Hypersplenism ; immunology ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Killer Cells, Natural ; drug effects ; immunology ; Liver Transplantation ; methods ; Lymphocyte Subsets ; drug effects ; immunology ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; administration & dosage ; therapeutic use ; Spleen ; drug effects ; immunology ; T-Lymphocytes, Regulatory ; drug effects ; immunology

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play crucial roles in a variety of diseases, including autoimmunity, infectious diseases, and cancers. However, little is known about the roles of these invariant T cells in acute cholecystitis. The purposes of this study were to examine the levels of MAIT cells and NKT cells in patients with acute cholecystitis and to investigate potential relationships between clinical parameters and these cell levels. Thirty patients with pathologically proven acute cholecystitis and 47 age- and sex-matched healthy controls were enrolled. Disease grades were classified according to the revised Tokyo guidelines (TG13) for the severity assessment for acute cholecystitis. Levels of MAIT and NKT cells in peripheral blood were measured by flow cytometry. Circulating MAIT and NKT cell numbers were significantly lower in acute cholecystitis patients than in healthy controls, and these deficiencies in MAIT cells and NKT cell numbers were associated with aging in acute cholecystitis patients. Notably, a reduction in NKT cell numbers was found to be associated with severe TG13 grade, death, and high blood urea nitrogen levels. The study shows numerical deficiencies of circulating MAIT and NKT cells and age-related decline of these invariant T cells. In addition, NKT cell deficiency was associated with acute cholecystitis severity and outcome. These findings provide an information regarding the monitoring of these changes in circulating MAIT and NKT cell numbers during the course of acute cholecystitis and predicting prognosis.
Aged ; Antibodies, Monoclonal/immunology ; Case-Control Studies ; Cholecystitis, Acute/*diagnosis/immunology/pathology ; Female ; Flow Cytometry ; Humans ; Leukocytes, Mononuclear/cytology ; Male ; Middle Aged ; Natural Killer T-Cells/*cytology/immunology ; Patients ; Prognosis ; Severity of Illness Index ; T-Lymphocyte Subsets/*cytology/immunology