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

Recent studies in man and animal models have demonstrated that TCR-gamma delta-bearing T cells (gamma delta T cells) are activated by mycobacteria and accumulate in the sites of mycobacterial infection. Although the function of gamma delta T cells remains unclear, some data suggest a potential role for these cells in the granulomatous immune response. To address the presence of gamma delta T cells within the BCG granulomas, we have characterized the TCR phenotype of T-lymphocytes present in the BCG granulomatous lesion immunohistochemically using a monoclonal antibody to TCR delta 1 and others. Fairly large numbers of gamma delta T cells were located at the periphery of the BCG granulomas without necrosis and most of them also expressed CD8. However, gamma delta T cells were rarely present in the granulomas with central caseous necrosis, calcification and fibrotic changes. With these results, it might be speculated that the CD8+ gamma delta T lymphocytes participate in the BCG granuloma formation mainly in the early stage.
Female ; Granuloma/immunology/*pathology ; Human ; Infant ; Lymph Nodes/pathology ; Male ; *Mycobacterium bovis ; Receptors, Antigen, T-Cell, gamma-delta/*analysis ; T-Lymphocytes/*immunology ; Tuberculosis/immunology/*pathology

To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD68. Nine cases of nonspecific tubulointerstitial change and 4 cases of nonallograft tubulointerstitial nephritis were used as a control. Inflammatory infiltration was present in all cases studied. T cells predominated in the interstitium of chronic rejection and were followed by macrophages and B cells. The degree of interstitial infiltration of frozen section was not accordant with that of paraffin sections. Allografts with nonspecific tubulointerstitial changes or tubulointerstitial nephritis of native kidneys showed similar distribution pattern in terms of type and degree. However, the degree of infiltrate did not give any statistical significance among groups. The CD4/CD8 ratios in interstitial infiltrates were less than 1.0 in 6 cases and was not accordant with those of peripheral blood. Proportion of nudelta T cells increased over 10% in 2 cases in tissue and in 3 cases in peripheral blood. In 3 cases of chronic rejection in which both tissue and blood results were available, there was no concordance of CD4/CD8 or nudeltaT/CD3 between them. Tubular expression of HLA DR was, however, present only in 4 cases of chronic rejection. In conclusion, T lymphocytes were predominant regardless of diagnosis or disease activity. T lymphocyte subset did not give any suggestion as to the diagnosis or disease activity in chronic rejection. Furthermore nudelta T cells had only limited value. Lymphocytic subsets in peripheral blood would not be predictors of tissue destruction in chronic rejection.
Flow Cytometry ; Graft Rejection/*immunology ; Human ; Kidney/cytology/*immunology ; Kidney Transplantation/*immunology ; Leukocytes, Mononuclear/*immunology ; Phenotype ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Support, Non-U.S. Gov't

To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD68. Nine cases of nonspecific tubulointerstitial change and 4 cases of nonallograft tubulointerstitial nephritis were used as a control. Inflammatory infiltration was present in all cases studied. T cells predominated in the interstitium of chronic rejection and were followed by macrophages and B cells. The degree of interstitial infiltration of frozen section was not accordant with that of paraffin sections. Allografts with nonspecific tubulointerstitial changes or tubulointerstitial nephritis of native kidneys showed similar distribution pattern in terms of type and degree. However, the degree of infiltrate did not give any statistical significance among groups. The CD4/CD8 ratios in interstitial infiltrates were less than 1.0 in 6 cases and was not accordant with those of peripheral blood. Proportion of nudelta T cells increased over 10% in 2 cases in tissue and in 3 cases in peripheral blood. In 3 cases of chronic rejection in which both tissue and blood results were available, there was no concordance of CD4/CD8 or nudeltaT/CD3 between them. Tubular expression of HLA DR was, however, present only in 4 cases of chronic rejection. In conclusion, T lymphocytes were predominant regardless of diagnosis or disease activity. T lymphocyte subset did not give any suggestion as to the diagnosis or disease activity in chronic rejection. Furthermore nudelta T cells had only limited value. Lymphocytic subsets in peripheral blood would not be predictors of tissue destruction in chronic rejection.
Flow Cytometry ; Graft Rejection/*immunology ; Human ; Kidney/cytology/*immunology ; Kidney Transplantation/*immunology ; Leukocytes, Mononuclear/*immunology ; Phenotype ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Support, Non-U.S. Gov't

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.
Antigens, Bacterial ; immunology ; Cell Separation ; methods ; Flow Cytometry ; Humans ; Mycobacterium tuberculosis ; immunology ; Receptors, Antigen, T-Cell, gamma-delta ; analysis ; T-Lymphocyte Subsets ; cytology

OBJECTIVETo investigate the percentages of peripheral blood γδ 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 γδ 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

Humans ; Liver Neoplasms ; genetics ; immunology ; pathology ; Lymphoma, T-Cell ; genetics ; immunology ; pathology ; Receptors, Antigen, T-Cell, alpha-beta ; metabolism ; Receptors, Antigen, T-Cell, gamma-delta ; metabolism ; Splenic Neoplasms ; genetics ; immunology ; pathology

OBJECTIVETo investigate the distribution and clonality of T cell receptor (TCR) V&gamma; and V&delta; subfamily in peripheral blood of patients with allergic rhinitis before and after 1 year treatment with immunotherapy.

METHODSThe specific IgE and the complementary determinant region 3 (CDR3) of TCR V &gamma; (I-III) and V&delta;(1-8) subfamily genes in mononuclear cells were amplified from 10 effective cases of allergic rhinitis before and after 1 year treatment with immunotherapy, to observe the distribution and utilization of TCR V&gamma; and V&delta; repertoire. The positive PCR products were further labeled with RT-PCR and analyzed by gene scan technique to determine the CDR3 size and evaluate the clonality of the detectable TCR V&gamma; and V&delta; T cells. Peripheral blood of 10 healthy adults served as controls.

RESULTSAll symptoms were significantly improved after 1 year specific immunotherapy, but no changes were seen in specific IgE [(22.89 ± 9.60) kU/L before treatment, (19.62 ± 7.63) kU/L after treatment, Z = 1.051, P > 0.05]. No statistically significant differences of expression levels of the TCR V&gamma; I-III subfamily genes were found between patients with allergic rhinitis normal control group (t value were -0.679, -0.516, -0.808, all P > 0.05), but significantly decreased after 1 year treatment. There were statistically significant differences of expression levels of the TCR V&gamma;I-II subfamily genes before and after treatment (t value were -2.904, -2.217, all P < 0.05). 5.30 ± 0.82, 4.90 ± 0.57 and 5.20 ± 1.40 out of TCR V&delta; (1-8) subfamilies were selectively expressed in T cells in patients with allergic rhinitis before and after 1 year treatment and normal control group, predominantly for TCR V&delta; 1, 2, 3 and 6. The TCR V&delta; 6 subfamily was found to have statistically significant differences in these groups (Fisher's Exact Test, P < 0.05). Compared with the normal control group and the allergic rhinitis group before treatment, a significant higher frequency of V&delta; 6 oligoclonal was identified in T cells in patients with allergic rhinitis after 1 year treatment.

CONCLUSIONSThere was difference in the expression levels of the TCR V&gamma; I-III subfamily genes and distribution and clonality of TCR V&gamma; and V&delta; subfamily T cells in peripheral blood of patients with allergic rhinitis before and after 1 year treatment. Specific immunotherapy can be effective in alleviation of the symptom in patients with allergic rhinitis during the early stage, possibly by inducing TCR &gamma;&delta; T cells, especially the TCR V&delta;6 subfamily, and possibly no significant relativity between symptom and specific IgE.

Adolescent ; Adult ; Case-Control Studies ; Female ; Genes, T-Cell Receptor ; Humans ; Immunoglobulin E ; blood ; Immunotherapy ; Male ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; immunology ; Receptors, Antigen, T-Cell, gamma-delta ; genetics ; immunology ; Rhinitis ; genetics ; immunology ; therapy ; Young Adult

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*

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