scholarly journals Alterations in Gamma-Delta T Cells in Patients With Primary Biliary Cholangitis

2021 ◽  
Author(s):  
Sha Chen ◽  
Tingting Lv ◽  
Guangyong Sun ◽  
Shuxiang Li ◽  
Weijia Duan ◽  
...  
Keyword(s):  
T Cells ◽  
Flow Cytometric Analysis ◽  
Γδ T Cells ◽  
Absolute Number ◽  
Primary Biliary Cholangitis ◽  
Gamma Delta ◽  
Potential Marker ◽  
Hla Dr ◽  
Tnf Α ◽  
Elevated Expression

Abstract Background & Aims Gamma-delta (γδ) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of γδ T cells in primary biliary cholangitis (PBC) remains unclear. Methods We analyzed the number, phenotypes, and functional molecules of γδ T cells in PBC patients (n = 74) and sex- and age-matched healthy controls (HCs) (n = 74) by flow cytometric analysis. Results We identified two distinct functional subsets of circulating γδ T cells according to the CD3/TCRγδ complex: the TCRγδhigh and TCRγδlow subsets. Approximately three-quarters of cells in the TCRγδhigh subset were Vδ1 T cells, while Vδ2 T cells were enriched in the TCRγδlow subset in HCs. The frequency and absolute number of circulating TCRγδlow cells was significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCRγδlow cells was negatively correlated with disease severity and positively correlated with the ursodeoxycholic acid response. TCRγδlow cells exhibited a similar apoptotic and proliferative phenotype but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, both TCRγδhigh and TCRγδlow subsets were more activated in PBC compared with HCs, characterized by elevated expression levels of CD69 and HLA-DR. Finally, we found an increased granzyme B (GZMB) production and similar IFN-γ and TNF-α production of TCRγδlow cells in PBC patients compared with HCs. Conclusion The TCRγδlow subset might be a potential marker for disease progression and treatment response in PBC, which may play a crucial role in liver injury through increased CXCR6 expression and GZMB production.

CD56+ human blood dendritic cells effectively promote TH1-type γδ T-cell responses

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4422-4431 ◽  
Author(s):  
Georg Gruenbacher ◽  
Hubert Gander ◽  
Andrea Rahm ◽  
Walter Nussbaumer ◽  
Nikolaus Romani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Γδ T Cells ◽  
Rapid Expansion ◽  
Γδ T Cell ◽  
Hla Dr ◽  
Tnf Α ◽  
Ifn Γ

Abstract CD56+ human dendritic cells (DCs) have recently been shown to differentiate from monocytes in response to GM-CSF and type 1 interferon in vitro. We show here that CD56+ cells freshly isolated from human peripheral blood contain a substantial subset of CD14+CD86+HLA-DR+ cells, which have the appearance of intermediate-sized lymphocytes but spontaneously differentiate into enlarged DC-like cells with substantially increased HLA-DR and CD86 expression or into fully mature CD83+ DCs in response to appropriate cytokines. Stimulation of CD56+ cells containing both DCs and abundant γδ T cells with zoledronate and interleukin-2 (IL-2) resulted in the rapid expansion of γδ T cells as well as in IFN-γ, TNF-α, and IL-1β but not in IL-4, IL-10, or IL-17 production. IFN-γ, TNF-α, and IL-1β production were almost completely abolished by depleting CD14+ cells from the CD56+ subset before stimulation. Likewise, depletion of CD14+ cells dramatically impaired γδ T-cell expansion. IFN-γ production could also be blocked by neutralizing the effects of endogenous IL-1β and TNF-α. Conversely, addition of recombinant IL-1β, TNF-α, or both further enhanced IFN-γ production and strongly up-regulated IL-6 production. Our data indicate that CD56+ DCs from human blood are capable of stimulating CD56+ γδ T cells, which may be harnessed for immunotherapy.

scholarly journals Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A Short Report

2021 ◽  
Vol 11 (16) ◽  
pp. 7325
Author(s):  
Dorota Pawlik-Gwozdecka ◽  
Justyna Sakowska ◽  
Maciej Zieliński ◽  
Magdalena Górska-Ponikowska ◽  
Francesco Cappello ◽  
...  
Keyword(s):  
T Cells ◽  
Strong Association ◽  
Γδ T Cells ◽  
Diagnostic Methods ◽  
Enzyme Linked Immunosorbent Assay ◽  
Short Report ◽  
Gamma Delta ◽  
Childhood All ◽  
Hla Dr ◽  
Shock Proteins

HSPs demonstrate a strong association with gamma-delta (γδ) T cells. Most of the studies regarding interactions between the parameters were conducted in the 1990s. Despite promising results, the concept of targeting γδ T cells by HSPs seems to be a forgotten direction due to potent non-peptidic phosphoantigens rather than HSPs have been found to be the essential stimulatory components for human γδ cells. Currently, with greater knowledge of lymphocyte diversity, and more accurate diagnostic methods, we decided to study the correlation once again in the neoplastic condition. Twenty-one children with newly diagnosed acute lymphoblastic leukaemia (ALL) were enrolled on the study. Serum HSP90 concentrations were evaluated by an enzyme-linked immunosorbent assay (ELISA), subsets of γδ T cells (CD3+ γδ, CD3+ γδ HLA/DR+, CD4+ γδ and CD8+ γδ) by flow cytometry. We have shown statistically relevant correlations between serum HSP90 and CD3+ HLA/DR+ γδ T cells in paediatric ALL at diagnosis (R = 0.53, p < 0.05), but not after induction chemotherapy. We also have demonstrated decreased levels of both serum HSP90 and CD3+ HLA/DR+ γδ T cells before treatment, which may indirectly indicate dose-dependent unknown interaction between the parameters. The results of our study may be a good introduction to research on the association between HSPs and CD3+ HLA/DR+ γδ T cells, which could be an interesting direction for the development of anti-cancer strategies, not just for childhood ALL.

scholarly journals Correlation between the Numbers of .GAMMA..DELTA. T Cells and CD4+HLA-DR+ T Cells in Broncho-Alveolar Lavage Fluid from Patients with Diffuse Lung Disease.

2002 ◽  
Vol 196 (4) ◽  
pp. 231-240 ◽  
Author(s):  
EIICHI SUZUKI ◽  
HIROKI TSUKADA ◽  
TAKASHI ISHIDA ◽  
OSAMU ISHIZUKA ◽  
TAKASHI HASEGAWA ◽  
...  
Keyword(s):  
T Cells ◽  
Lung Disease ◽  
Lavage Fluid ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Diffuse Lung Disease ◽  
Hla Dr ◽  
Diffuse Lung

Characterization of γδ T Cells in Intestinal Mucosa From Patients With Early-Onset or Long-Standing Inflammatory Bowel Disease and Their Correlation With Clinical Status

2019 ◽  
Vol 13 (7) ◽  
pp. 873-883 ◽  
Author(s):  
Elena Lo Presti ◽  
Roberto Di Mitri ◽  
Filippo Mocciaro ◽  
Anna Barbara Di Stefano ◽  
Nunzia Scibetta ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Intestinal Mucosa ◽  
Bowel Disease ◽  
Early Onset ◽  
Γδ T Cells ◽  
Healthy Tissue ◽  
Effector Memory ◽  
Tnf Α ◽  
Inflammatory Bowel

Abstract Background and Aims Inflammatory bowel disease [IBD] is a complex chronic inflammatory disease of the human gut with no clear aetiology. Traditionally, dysregulated adaptive immune responses play an important role even though accumulating evidence suggests a role also for innate immunity. Because of the well-known plasticity of γδ T cells, we investigated their percentage occurrence, phenotypic features and effector functions in the intestinal mucosa of early-onset and long-standing IBD patients, as compared to healthy subjects. Methods Fresh biopsies from 30 Crohn’s disease and ulcerative colitis patients were obtained and digested, and cells were analysed by flow cytometry. Results We found a reduced frequency of Vδ1 T cells in tissue from early and late IBD patients (2.24% and 1.95%, respectively, vs 5.44% in healthy tissue) but an increased frequency of Vδ2 T cells in the gut of late IBD patients (3.19% in late patients vs 1.5% in early patients and 1.65% in healthy tissue). The infiltrating Vδ2 T cells had predominant effector memory and terminally differentiated phenotypes and produced elevated levels of tumour necrosis factor-α [TNF-α] and interleukin-17 [IL-17]. The frequency of tissue Vδ2 T cells correlated with the extent of the inflammatory response and the severity of IBD. Conclusion Our study shows that tissue Vδ1 T cells are decreased in IBD patients while Vδ2 T cells are increased in the gut of IBD patients and contribute to TNF-α production. Moreover, we identify an as yet unappreciated role of Vδ2 T cells in IL-17 production in the gut of long-standing IBD patients, suggesting that they also participate in the chronic inflammatory process.

scholarly journals γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury

2017 ◽  
Vol 215 (2) ◽  
pp. 521-535 ◽  
Author(s):  
Guodong Sun ◽  
Shuxian Yang ◽  
Guangchao Cao ◽  
Qianghua Wang ◽  
Jianlei Hao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
T Cells ◽  
Functional Recovery ◽  
Γδ T Cells ◽  
Small Subset ◽  
Cell Functions ◽  
Tnf Α ◽  
Cord Injury ◽  
Ifn Γ

Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ−/−) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ. Inactivating IFN-γ signaling in macrophages results in a significantly reduced production of proinflammatory cytokines in the cerebrospinal fluid (CSF) of mice with SCIs and improves functional recovery. Furthermore, treatment of SCI with anti-Vγ4 antibodies has a beneficial effect, similar to that obtained with anti–TNF-α. In SCI patients, γδ T cells are detected in the CSF, and most of them are IFN-γ positive. In conclusion, manipulation of γδ T cell functions may be a potential approach for future SCI treatment.

γδ T Cells Contribute to the Outcome of Murine Fulminant Viral Hepatitis via Effector Cytokines TNF-α and IFN-γ

2018 ◽  
Vol 38 (4) ◽  
pp. 648-655 ◽  
Author(s):  
Di Wu ◽  
Wei-ming Yan ◽  
Hong-wu Wang ◽  
Da Huang ◽  
Xiao-ping Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Hepatitis ◽  
Γδ T Cells ◽  
Fulminant Viral Hepatitis ◽  
Tnf Α ◽  
Ifn Γ ◽  
Effector Cytokines

scholarly journals High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity

Gut ◽  
2019 ◽  
Vol 69 (4) ◽  
pp. 691-703 ◽  
Author(s):  
Natasja L de Vries ◽  
Vincent van Unen ◽  
Marieke E Ijsselsteijn ◽  
Tamim Abdelaal ◽  
Ruud van der Breggen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Lymph Nodes ◽  
Single Cell ◽  
Immune Cell ◽  
Γδ T Cells ◽  
High Dimensional ◽  
Hla Dr ◽  
Healthy Mucosa ◽  
Immune Contexture

ObjectiveA comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC.DesignThirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence.ResultsWe discovered that a previously unappreciated innate lymphocyte population (Lin–CD7+CD127–CD56+CD45RO+) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103+CD69+) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR+CD38+PD-1+) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes.ConclusionThis work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.

scholarly journals PD-1 signaling modulates interferon-γ production by Gamma Delta (γδ) T-Cells in response to leukemia

2018 ◽  
Vol 8 (3) ◽  
pp. 1550618 ◽  
Author(s):  
Timm Hoeres ◽  
Elisabeth Holzmann ◽  
Manfred Smetak ◽  
Josef Birkmann ◽  
Martin Wilhelm
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Interferon Γ ◽  
Gamma Delta
Sign in / Sign up

Export Citation Format

Share Document