Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen's method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17⁺ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17⁺ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the "gut-spinal cord-immune" axis may be one of the mechanisms regulating neural repair after SCI.
Animals ; Rats ; Interleukin-17 ; Rats, Sprague-Dawley ; Recovery of Function ; Spinal Cord Injuries/drug therapy* ; T-Lymphocytes, Regulatory ; Receptors, Antigen, T-Cell, gamma-delta/immunology*

The γδ T cells are unconventional lymphocytes that function in both innate and adaptive immune responses against various intracellular and infectious stresses. The γδ T cells can be exploited as cancer-killing effector cells since γδ TCRs recognize MHC-like molecules and growth factor receptors that are upregulated in cancer cells, and γδ T cells can differentiate into cytotoxic effector cells. However, γδ T cells may also promote tumor progression by secreting IL-17 or other cytokines. Therefore, it is essential to understand how the differentiation and homeostasis of γδ T cells are regulated and whether distinct γδ T cell subsets have different functions. Human γδ T cells are classified into Vδ2 and non-Vδ2 γδ T cells. The majority of Vδ2 γδ T cells are Vγ9δ2 T cells that recognize pyrophosphorylated isoprenoids generated by the dysregulated mevalonate pathway. In contrast, Vδ1 T cells expand from initially diverse TCR repertoire in patients with infectious diseases and cancers. The ligands of Vδ1 T cells are diverse and include the growth factor receptors such as endothelial protein C receptor. Both Vδ1 and Vδ2 γδ T cells are implicated to have immunotherapeutic potentials for cancers, but the detailed elucidation of the distinct characteristics of 2 populations will be required to enhance the immunotherapeutic potential of γδ T cells. Here, we summarize recent progress regarding cancer immunology of human γδ T cells, including their development, heterogeneity, and plasticity, the putative mechanisms underlying ligand recognition and activation, and their dual effects on tumor progression in the tumor microenvironment.
Allergy and Immunology ; Communicable Diseases ; Cytokines ; Homeostasis ; Humans ; Interleukin-17 ; Ligands ; Lymphocytes ; Mevalonic Acid ; Plastics ; Population Characteristics ; Protein C ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, Growth Factor ; T-Lymphocyte Subsets ; T-Lymphocytes ; Terpenes ; Tumor Microenvironment

Objective 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. Methods 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. Results 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⁺ BTLA⁺γδT 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 PD1⁺γδ⁺ and BTLA⁺γδ⁺ 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). Conclusions 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.
Bone Neoplasms/secondary* ; CD8-Positive T-Lymphocytes ; Carcinoma, Non-Small-Cell Lung/immunology* ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ligands ; Lung Neoplasms/immunology* ; Lymphocyte Subsets/immunology* ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/metabolism* ; RNA, Messenger/metabolism* ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, Immunologic/metabolism*

OBJECTIVETo investigate the percentages of peripheral blood &gamma;&delta; T cells and regulatory T cells (Treg) and the expression of associated cytokines, interleukin 17 (IL-17) and transforming growth factor-β1 (TGF-β1), in infants with human cytomegalovirus (HCMV) infection.

METHODSTwenty-two infants with HCMV infection (HCMV group) and 22 healthy infants who underwent physical examination (control group) were enrolled in this study. The percentages of peripheral blood &gamma;&delta; T cells and Treg cells were determined by flow cytometry. The levels of IL-17 and TGF-β1 in plasma were measured using ELISA.

RESULTSCompared with the control group, the HCMV group had significantly higher percentage of &gamma;&delta; T cells and IL-17 level (P<0.01) and significantly lower percentage of Treg cells and TGF-β1 level (P<0.01). In the HCMV group, the percentage of &gamma;&delta; T cells was negatively correlated with the percentage of Treg cells and TGF-β1 level (P<0.05), but positively correlated with IL-17 level (P<0.05); the percentage of Treg cells was positively correlated with TGF-β1 level (P<0.05), but negatively correlated with IL-17 level (P<0.05); there was no correlation between IL-17 level and TGF-β1 level (P>0.05).

CONCLUSIONSThere is an imbalance between &gamma;&delta; T cells and Treg cells in the peripheral blood of infants with HCMV infection, and &gamma;&delta; T cells may be involved in the secretion of IL-17.

Cytokines ; blood ; Cytomegalovirus Infections ; immunology ; Female ; Humans ; Infant ; Interleukin-17 ; blood ; Male ; Receptors, Antigen, T-Cell, gamma-delta ; analysis ; T-Lymphocytes, Regulatory ; immunology ; Transforming Growth Factor beta1 ; blood

No abstract available.
Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B-Cell-Specific Activator Protein/metabolism ; Bone Marrow/metabolism/*pathology ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Endoscopy, Digestive System ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Genetic Loci ; Humans ; Liver/metabolism/pathology ; Lymphocytes/cytology/immunology ; Lymphoma, Large B-Cell, Diffuse/complications/*diagnosis/drug therapy ; Lymphoma, T-Cell, Peripheral/complications/*diagnosis/drug therapy ; Middle Aged ; Prednisone/therapeutic use ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

OBJECTIVETo investigate the role played by &gamma;&delta; T cells in acute liver injury using the concanavalin A (ConA)-induced liver injury mouse model.

METHODSAcute liver injury was induced by intravenous injection of 10 mug/g of ConA into male C57BL/6J mice with wild-type or T cell receptor-&gamma; knockout (TCR &delta;-/-) genetic backgrounds. Mice injected with PBS alone served as negative controls. The degree of liver damage was assessed by measuring serum levels of transaminase and cytokines at post-injection hours 3, 6, 12, 24, 48, and 72. The percentage of &gamma;&delta; T cells and proportions of different subsets in liver lymphocytes were measured by flow cytometry.

RESULTSThe TCR &delta;-/- mice showed significantly higher levels of the inflammatory cytokines IFN-&gamma;, TNFα and IL-4 than the wild-type mice at post-injection hour 3. The percentage of liver &gamma;&delta; T cells increased with increased injury degree, and the extent of increase was significantly higher in the TCR &delta;-/- mice than the wild-type mice (post-injection hour 6: 6302.61+/-592.06 vs. 1319.26+/-355.48, 12: 6569.44+/-1060.98 vs. 3415.53+/-343.90, 24: 6514.29+/-757.26 vs. 2062.73+/-365.67, 48: 1262.61+/-558.07 vs. 113.66+/-113.26, and 72: 226.54+/-98.20 vs. 42.35+/-21.51 U/L; all P less than 0.05). In addition, compared to the negative control mice, the ConA-induced mice showed a higher proportions of V&gamma;4 &gamma;&delta; T cells to total &gamma;&delta; T cells (17.78+/-2.95 vs. 25.26+/-2.43) and to total liver lymphocytes (0.47+/-0.07 vs. 0.66+/-0.05). Similarly, compared to the negative control mice, the ConA-induced mice showed a higher proportion of V&gamma;1 &gamma;&delta; T cells to total &gamma;&delta; T cells (38.37+/-6.10 vs. 50.19+/-5.52) but the proportion to total liver lymphocytes was not significantly different among the groups (0.76+/-0.18 vs. 0.78+/-0.25). Reinfusion of V&gamma;4 &gamma;&delta; T lymphocytes into TCR &delta;-/- mice led to lower serum ALT levels than reinfusion of V&gamma;1 &gamma;&delta; T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L).

CONCLUSION&gamma;&delta; T cells play a protective role in ConA-induced liver injury and this effect maybe mediated by the V&gamma;4 &gamma;&delta; T cell subset.

Animals ; Chemical and Drug Induced Liver Injury ; immunology ; pathology ; Concanavalin A ; toxicity ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Liver ; drug effects ; immunology ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell, gamma-delta ; metabolism ; T-Lymphocyte Subsets ; immunology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo investigate the cytotoxic effect of &gamma;&delta; T cells from osteosarcoma patients against interferon-&gamma; (IFN-&gamma;)-treated osteosarcoma cells in vitro.

METHODSHuman &gamma;&delta; T cells were amplified by zoledronate from peripheral blood cells of osteosarcoma patients. The expression of Fas on the osteosarcoma cells were measured by flow cytometry and quantitative real-time PCR analysis before and after IFN-&gamma; treatment. The cytotoxicity of &gamma;&delta; T cells against osteosarcoma cells was evaluated with LDH assay.

RESULTSIFN-&gamma; significantly enhanced the susceptibility of the osteosarcoma cell lines HOS and U2OS to the cytotoxicity of &gamma;Delta; T cells from osteosarcoma patients (P<0.01). IFN-&gamma; obviously up-regulated the expression of Fas in HOS and U2OS cells (P<0.01). Anti-FasL mAb failed to inhibit the cytotoxicity of &gamma;&delta; T cells in untreated osteosarcoma targets (P>0.05), but significantly impaired &gamma;&delta; T cell cytotoxicity in IFN-&gamma; pre-treated osteosarcoma targets (P<0.01).

CONCLUSIONIFN-&gamma; can enhance the cytotoxic effect of human &gamma;&delta; T cells from osteosarcoma patients against osteosarcoma cells in vitro.

Bone Neoplasms ; metabolism ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Humans ; Interferon-gamma ; pharmacology ; Osteosarcoma ; immunology ; metabolism ; Receptors, Antigen, T-Cell, gamma-delta ; immunology ; T-Lymphocytes, Cytotoxic ; cytology ; drug effects ; immunology ; fas Receptor ; metabolism

OBJECTIVETo analyze the changes in peripheral natural killer T-cells (NKT) and gammadelta T-cells (&gamma; &delta; T-cell) in patients with minimal residual leukemia (MRL) before and after being treated with Yiqi Bushen Granule (益气补肾颗粒, YBG) in order to determine their significance in prognosis of the disease. Granule (益气补肾颗粒, YBG) in order to determine their significance in prognosis of the disease.

METHODSBefore and after treatment, the changes in 36 patients (16 males and 20 females) receiving long-term (more than 3 months) YBG therapy were analyzed using multi-parameter flow cytometry, with 34 healthy persons (19 males and 15 females) acting as controls. males and 15 females) acting as controls.

RESULTSThe absolute value and percentage of NKT cells and &gamma; &delta; T-cells were all significantly raised after treatment, for NKT cells, 0.52%±0.39% to 0.83%±0.66% and 7.25±7.77 cells cell/μL to 12.86±11.99 cell/μL, for &gamma; &delta; T-cells, 6.08%±3.03% to 7.24%±2.78% and 83.97±48.09 cell/μL 110.53±54.12 cell/μL, respectively (P<0.05 or P<0.01).

CONCLUSIONYBG could regulate the immune function and elevate the amount of NKT cells and &gamma; &delta; T-cells, thus to kill or suppress the residual leukemic cell in the body, which might be one of the mechanisms of YBG in prolonging the disease-free survival in MRL patients.

Adult ; Aged ; Case-Control Studies ; Humans ; Killer Cells, Natural ; drug effects ; Leukemia ; immunology ; therapy ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm, Residual ; Receptors, Antigen, T-Cell, gamma-delta ; immunology

GammadeltaT cells are considered as linkage between innate and adaptive immune response, which recognize specific antigen without MHC-restriction. Vgamma9Vdelta2T cells, isolated from peripheral blood and tumor tissue, can be activated by non-peptide phosphoantigen through binding to its gammadeltaTCR and proliferate under IL-2 stimulation. It has been shown that Vgamma9Vdelta2T cells possess anticancer activity against several types of tumor in vitro, as well as inhibit the growth of lymphoma, breast cancer and malignant melanoma in vivo. The phase I clinical trial of the application of Vgamma9Vdelta2T cells in treatment of lung cancer, renal cancer and prostate cancer demonstrated promising results. This review summarizes the recent advances in antigen recognition and activation of gammadeltaT cells, and the gammadeltaT cell-based immunotherapy for cancer treatment.
Humans ; Immunotherapy ; methods ; Immunotherapy, Adoptive ; methods ; Neoplasms ; immunology ; therapy ; Receptors, Antigen, T-Cell, gamma-delta ; immunology ; T-Lymphocyte Subsets ; immunology

OBJECTIVETo observe the TCR V gamma gene repertoire diversity in the peripheral blood mononuclear cells of the patients with the chronic benzene poisoning.

METHODSComplementarity determining region 3 (CDR3) of TCR V gamma subfamily genes were amplified in 10 patients with the chronic benzene poisoning using RT-PCR. The PCR products were further analyzed by genescan to evaluate clonality of T cells. 8 healthy persons served as control.

RESULTSAll V gamma subfamilies were detected in the 8 healthy donors. (1.30 +/- 0.48) V gamma subfamilies were detected in 10 patients. The number of detectable V gamma subfamilies present in the patients with the chronic benzene poisoning was significantly lower than in the control group (P < 0.01). The most frequently used V gamma genes in clonally expanded T-cells were V gamma II.

CONCLUSIONSkewed distribution and clonal expansion of TCR V gamma subfamily T cells could be found in the patients with the chronic benzene poisoning. This is the first report of clonal expansion TCR V gamma T cells in patients with chronic benzene poisoning. The bias pattern of TCR V alpha T cells may be due to the immune cytotoxicity from benzene.

Adult ; Benzene ; poisoning ; Chronic Disease ; Complementarity Determining Regions ; genetics ; Female ; Humans ; Leukocytes, Mononuclear ; immunology ; Male ; Middle Aged ; Occupational Diseases ; genetics ; immunology ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; immunology ; Young Adult