Increased Proportions of Peripheral Blood γδ T Cells in Patients with Pulmonary Tuberculosis

CHEST Journal ◽  
1992 ◽  
Vol 102 (1) ◽  
pp. 195-197 ◽  
Author(s):  
Masami Ito ◽  
Naoyoshi Kojiro ◽  
Toshiyuki Ikeda ◽  
Takashi Ito ◽  
Junichi Funada ◽  
...  
2008 ◽  
Vol 5 (3) ◽  
pp. 203-208 ◽  
Author(s):  
Meiyu Peng ◽  
Zhaohua Wang ◽  
Chunyan Yao ◽  
Lina Jiang ◽  
Qili Jin ◽  
...  

2013 ◽  
Vol 20 (4) ◽  
pp. 530-539 ◽  
Author(s):  
Xueyan Xi ◽  
Xiqin Han ◽  
Liang Li ◽  
Zhendong Zhao

ABSTRACTThe immune protection initiated by γδ T cells plays an important role in mycobacterial infection. The γδ T cells activated byMycobacterium tuberculosis-derived nonpeptidic, phosphorylated biometabolites (phosphoantigens) provide only partial immune protection against mycobacterium, while evidence has suggested that protein antigen-activated γδ T cells elicit effective protective immune responses. To date, only a few distinct mycobacterial protein antigens have been identified. In the present study, we screened protein antigens recognized by γδ T cells using cells transfected with the predominant pulmonary tuberculosis γδ T cell receptor (TCR) CDR3 fragment. We identified two peptides, TP1 and TP2, which not only bind to the pulmonary tuberculosis predominant γδ TCR but also effectively activate γδ T cells isolated from pulmonary tuberculosis patients. Moreover, 1-deoxy-d-xylulose 5-phosphate synthase 2 (DXS2), the TP1-matched mycobacterial protein, was confirmed as a ligand for the γδ TCR and was found to activate γδ T cells from pulmonary tuberculosis patients. The extracellular region (extracellular peptide [EP]) of Rv2272, a TP2-matched mycobacterial transmembrane protein, was also shown to activate γδ T cells from pulmonary tuberculosis patients. Both DXS2- and EP-expanded γδ T cells from pulmonary tuberculosis patients could secrete gamma interferon (IFN-γ) and monocyte chemoattractant protein 1 (MCP-1), which play important roles in mediating cytotoxicity against mycobacterium and stimulating monocyte chemotaxis toward the site of infection. In conclusion, our study identified novel mycobacterial protein antigens recognized by γδ TCR cells that could be candidates for the development of vaccines or adjuvants against mycobacterium infection.


2006 ◽  
Vol 74 (7) ◽  
pp. 3967-3978 ◽  
Author(s):  
Angela Berndt ◽  
Jana Pieper ◽  
Ulrich Methner

ABSTRACT γδT cells are considered crucial to the outcome of various infectious diseases. The present study was undertaken to characterizeγδ (T-cell receptor 1+ [TCR1+]) T cells phenotypically and functionally in avian immune response. Day-old chicks were orally immunized with Salmonella enterica serovar Enteritidis live vaccine or S. enterica serovar Enteritidis wild-type strain and infected using the S. enterica serovar Enteritidis wild-type strain on day 44 of life. Between days 3 and 71, peripheral blood was examined flow cytometrically for the occurrence of γδ T-cell subpopulations differentiated by the expression of T-cell antigens. Three different TCR1+ cell populations were found to display considerable variation regarding CD8α antigen expression: (i) CD8α+high TCR1+ cells, (ii) CD8α+dim TCR1+ cells, and (iii) CD8α− TCR1+ cells. While most of the CD8α+high TCR1+ cells expressed the CD8αβ heterodimeric antigen, the majority of the CD8α+dim TCR1+ cells were found to express the CD8αα homodimeric form. After immunization, a significant increase of CD8αα+high γδ T cells was observed within the CD8α+high TCR1+ cell population. Quantitative reverse transcription-PCR revealed reduced interleukin-7 receptor α (IL-7Rα) and Bcl-x expression and elevated IL-2Rα mRNA expression of the CD8αα+highγδ T cells. Immunohistochemical analysis demonstrated a significant increase of CD8α+ and TCR1+ cells in the cecum and spleen and a decreased percentage of CD8β+ T cells in the spleen after Salmonella immunization. After infection of immunized animals, immune reactions were restricted to intestinal tissue. The study showed that Salmonella immunization of very young chicks is accompanied by an increase of CD8αα+high γδ T cells in peripheral blood, which are probably activated, and thus represent an important factor for the development of a protective immune response to Salmonella organisms in chickens.


Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 992-1001 ◽  
Author(s):  
Daniel V. Correia ◽  
Manuela Fogli ◽  
Kelly Hudspeth ◽  
Maria Gomes da Silva ◽  
Domenico Mavilio ◽  
...  

Abstract The success of cancer immunotherapy depends on productive tumor cell recognition by killer lymphocytes. γδ T cells are a population of innate-like lymphocytes endowed with strong, MHC-unrestricted cytotoxicity against tumor cells. This notwithstanding, we recently showed that a large proportion of human hematologic tumors is resistant to γδ peripheral blood lymphocytes (PBLs) activated with specific agonists to the highly prevalent Vγ9Vδ2 TCR. Although this probably constitutes an important limitation to current γδ T cell–mediated immunotherapy strategies, we describe here the differentiation of a novel subset of Vδ2− Vδ1+ PBLs expressing natural cytotoxicity receptors (NCRs) that directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells. We show that Vδ1+ T cells can be selectively induced to express NKp30, NKp44 and NKp46, through a process that requires functional phosphatidylinositol 3-kinase (PI-3K)/AKT signaling on stimulation with γc cytokines and TCR agonists. The stable expression of NCRs is associated with high levels of granzyme B and enhanced cytotoxicity against lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition. Thus, NKp30+ Vδ1+ T cells constitute a novel, inducible and specialized killer lymphocyte population with high potential for immunotherapy of human cancer.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 902-902
Author(s):  
Li Xuan ◽  
Xiuli Wu ◽  
Sijian Yu ◽  
Zhengshan Yi ◽  
Yu Zhang ◽  
...  

Abstract Background The immune modulatory effect of granulocyte colony-stimulating factor (G-CSF) on T cells resulted in an unexpected low incidence of graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation. Our previous studies demonstrated that G-CSF mobilization influenced the distribution and clonality of TRGV and TRDV repertoire (T cell receptors of γδ T cells), and significant positive correlation was observed between the invariable clonality of TRDV1 gene repertoire after G-CSF mobilization and low incidence of GVHD in recipients (P=0.015, OR=0.047) (Li Xuan et al. Journal of Translational Medicine 2011). Regulatory γδ T cells (γδ Tregs), which express Foxp3 and primarily belong to CD27+CD25high phenotype, are a novel subset of cells with immunosuppressive function (Xiaoyan Li et al. Journal of Immunology 2012). However, whether G-CSF could influence the expression of γδ Tregs remains unknown. The aim of this study was to investigate the effect of G-CSF mobilization on the expression of γδ Tregs. Methods The immunophenotyping of γδ Tregs was analyzed in peripheral blood mononuclear cells (PBMCs) from 20 donors before and after G-CSF mobilization, using flow cytometry. Results Compared with that before mobilization, the proportions of Vδ1 and CD25+ subsets were significantly increased (P=0.012, P=0.032), whereas the Vδ2 proportion was significantly decreased after G-CSF mobilization (P=0.002). The proportions of total γδ T cells, CD27+ and Foxp3+ subsets were similar between the two groups (P=0.133, P=0.110, P=0.780, respectively). In addition, there was a significant increase in the proportions of Foxp3+Vδ1 and CD25+Foxp3+ subsets (P=0.038, P=0.013), and a significant decrease in the proportions of CD27+Vδ2 and CD25+Vδ2 subsets after G-CSF mobilization (P=0.013, P=0.022). The proportions of CD27+γδ T, CD25+γδ T, Foxp3+γδ T, CD25+CD27+, CD27+Foxp3+, CD27+Vδ1, CD25+Vδ1 and Foxp3+Vδ2 subsets were similar before and after G-CSF mobilization (P=0.422, P=0.342, P=0.724, P=0.070, P=0.503, P=0.053, P=0.386 and P=0.097, respectively). We then compared the Foxp3, CD27 and CD25 phenotypes in total γδ T cells, Vδ1 and Vδ2 subsets. We observed a significant increase in the proportion of CD27+Foxp3+ Vδ1 subsets after G-CSF mobilization (P=0.036). The proportion of CD27+Foxp3+γδ T and CD27+Foxp3+Vδ2 subsets before mobilization were similar to that after mobilization (P=0.539, P=0.507). The proportion of CD25+Foxp3+γδ T, CD25+Foxp3+ Vδ1, CD25+Foxp3+Vδ2, CD25+CD27+γδT, CD25+CD27+Vδ1 and CD25+CD27+ Vδ2 subsets were also similar between the two groups (P=0.249, P=0.539, P=0.507, P=0.934, P=0.209 and P=0.061, respectively). Conclusions G-CSF mobilization significantly increased the proportions of Vδ1 subsets, including Foxp3+Vδ1 and CD27+Foxp3+ Vδ1 subsets, whereas decreased the Vδ2 proportion. Disclosures: Li: This work was supported by Grants from National Natural Science Foundation of China (30871091 and 91129720), the Collaborated grant for HK-Macao-TW of Ministry of Science and Technology (2012DFH30060), the Guangdong Science & Technology Project (2012B0506: Research Funding. Liu: It was supported by 863 Program (No. 2011AA020105).: Research Funding; It was supported by National Public Health Grand Research Foundation (Grant No. 201202017), National Natural Science Foundation of China (Grant No.81000231, No.81270647).: Research Funding; It was supported by Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.


2009 ◽  
Vol 8 (16) ◽  
pp. 1540-1549 ◽  
Author(s):  
Ning Kang ◽  
Jianhua Zhou ◽  
Tie Zhang ◽  
Lifang Wang ◽  
Fang Lu ◽  
...  

1997 ◽  
Vol 8 (1) ◽  
pp. 76-89 ◽  
Author(s):  
A. Mathur ◽  
B.S. Michalowicz

The adaptive immune system consists of humoral and cell-mediated immunity. T-lymphocytes are the key components of cell-mediated immunity. CD4+ helper T-lymphocytes facilitate B-cells to differentiate and produce specific antibodies, whereas CD8+ cytotoxic T-lymphocytes kill virally infected cells. Periodontal diseases have been associated with a variety of imbalances in the regulation of immune responses. Changes in the ratios of peripheral blood CD4+ and CD8+ T-lymphocytes, depressed proliferative responses of peripheral blood lymphocytes, and increased frequency of CD45RO+ memory T-lymphocytes in diseased tissues have been reported in individuals with various forms of periodontal disease. While some studies have shown an increased frequency of γδ+ T-cells in periodontal lesions, the role of γδ+ T-cells in periodontal disease remains controversial. The ability of putative periodontopathic bacteria selectively to stimulate certain V(3-expressing T-cells is intriguing and could determine whether a CD4+ Th I or a CD4+ Th2 cell response is elicited. The prominence of a particular subset of helper T-cells within the periodontal lesion could be a reflection of the stage and activity of the disease, or the types of bacteria present. Regardless, longitudinal studies of the involvement of T-cell subsets and cytokines in periodontal disease are clearly needed.


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