Chronic Clonal Proliferative Disease of Gamma-Delta (γδ) T-cells in a Patient with Rheumatoid Arthritis and Neutropenia: Lack of the Morphology and the Immunophenotype of Large Granular Lymphocytes

2004 ◽  
Vol 45 (9) ◽  
pp. 1935-1937 ◽  
Author(s):  
I Pérez Sánchez ◽  
J López Longo ◽  
A Escudero Soto ◽  
J Gil Herrera ◽  
J Anguita Velaso ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Γδ T Cells ◽  
Large Granular Lymphocytes ◽  
Gamma Delta ◽  
Proliferative Disease ◽  
Granular Lymphocytes

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.

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

scholarly journals Characterization of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis

1986 ◽  
Vol 29 (5) ◽  
pp. 675-679 ◽  
Author(s):  
Bernard Combe ◽  
Monique Andary ◽  
Jean Caraux ◽  
Pierre Baldet ◽  
Françoise Barchechath ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Large Granular Lymphocytes ◽  
Granular Lymphocytes

scholarly journals Differential Activation of V γ4V δ1 and V γ9V δ2 Cord Blood Derived Gamma Delta T Cells upon Exposure to EBV-Lcl and K562 Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2790-2790
Author(s):  
Jeremy Wee Kiat Ng ◽  
Joey Lai ◽  
Tony Kiat Hon Lim ◽  
William YK Hwang ◽  
Shang Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Single Cell ◽  
Γδ T Cells ◽  
Rapid Expansion ◽  
Leukemia Cell Line ◽  
Γδ T Cell ◽  
Gamma Delta

Abstract Gamma-delta (γδ) T cells have emerged as a promising candidate for adoptive cellular immunotherapy. To harness and maximize the anti-leukemia properties of these cells, we sort to comprehensively profile the transcriptomic signatures and immune repertoire of in vitro expanded γδ T cell products. Given the reported diverse TCR γδ repertoire and naïve nature of γδ T cells found in human cord blood (CB γδ), we serially track the molecular and cellular changes in these cells upon activation in expansion cultures. Based on the established viral reactivities of γδ T cell as well as prior studies showing their cross reactivities against leukemia and cancer cells, we had previously shown that stimulating CB γδ with an irradiated EBV-LCL feeder cell-based rapid expansion protocol (REP) is capable of generating cell products with potent and specific cytotoxicity against human AML cells. In the present study, using single cell RNA sequencing (scRNA-seq) coupled with single cell TCR γδ repertoire analysis, we compared the transcription signatures between our REP expanded γδ T cell (REP γδ) and non-manipulated γδ T cells reported in literatures, showing the progressive acquisition of an adult PB derived γδ T cell (PB γδ)-like cell states. Time course analysis demonstrated complex T cell activation and maturation trajectories correlating with variable level of clonal induction throughout the course of in vitro expansion. At the end of expansion, the harvested REP γδ are predominantly of the V γ4V δ1 subtype. Nevertheless, upon exposing REP γδ to target leukemia cell line K562, outgrowth of other non-V γ4V δ1 as well as the semi-invariant V γ9V δ2 cells were observed. Taken together, our data shows that as CB γδ expand and differentiate in culture, they adopt an adult PB γδ-like program. More importantly, our data highlights the rich clonal composition of in vitro expanded CB γδ, with different clonotypes being variably activated upon exposure to different stimuli. Such characteristics can potentially overcome the challenges of cancer heterogeneity and cell persistence, with the potential of improving outcomes in cell immunotherapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Mycobacterium avium-intracellulare induces interleukin-6 from human monocytes and large granular lymphocytes

Blood ◽  
1991 ◽  
Vol 77 (10) ◽  
pp. 2218-2224 ◽  
Author(s):  
DK Blanchard ◽  
MB Michelini-Norris ◽  
CA Pearson ◽  
CS Freitag ◽  
JY Djeu
Keyword(s):  
T Cells ◽  
Mycobacterium Avium ◽  
Interleukin 6 ◽  
Mononuclear Cells ◽  
Human Leukocyte ◽  
Large Granular Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Mycobacterium Avium Intracellulare ◽  
Culture Supernatants ◽  
Granular Lymphocytes

Abstract Mycobacterium avium-intracellulare (MAI) is an opportunistic pathogen commonly found in acquired immunodeficiency syndrome patients, whose immune systems are severely compromised. However, normal responses to this bacterium are apparently sufficient to prevent disseminated infection because disease is rarely found unless an immunocompromised state is present. Because interleukin-6 (IL-6) is an inflammatory cytokine with a multitude of activities, we investigated the potential of MAI to induce IL-6 from normal human leukocytes. Peripheral blood mononuclear cells were fractionated into monocytes (Mo), large granular lymphocytes (LGL), and T cells and stimulated with bacteria. Culture supernatants were collected and assayed for IL-6 activity by bioassay. Mo and LGL, but not T cells, were found to release IL-6 within 12 hours of stimulation, with optimal production occurring by 2 days of culture. Production of IL-6 from human leukocyte subsets was confirmed by Northern blot analysis and by neutralization of biologic function of the culture supernatants with specific antisera. Taken together, these results indicate that production of IL-6 is a key response of Mo and LGL to MAI. The role of IL-6 in MAI infection, therefore, needs to be further investigated.

scholarly journals Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

2022 ◽  
Vol 12 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Tatsukuni Ohno ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Mouse Model ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Micro Ct ◽  
Layer Width ◽  
Temporomandibular Joints ◽  
Histological Staining

Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

scholarly journals Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity

2021 ◽  
Vol 11 ◽  
Author(s):  
Gokul Raj Kathamuthu ◽  
Nathella Pavan Kumar ◽  
Kadar Moideen ◽  
Pradeep A. Menon ◽  
Subash Babu
Keyword(s):  
T Cells ◽  
Latent Tuberculosis ◽  
Γδ T Cells ◽  
Positive Control ◽  
Gamma Delta ◽  
Immune Markers ◽  
Antigen Stimulation ◽  
Significant Difference ◽  
Control Antigen ◽  
Th17 Cytokine

Antigen-specific gamma-delta (γδ) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and positive control antigen-stimulated γδ T cells expressing Th1 (IFNγ, TNFα, IL-2) and Th17 (IL-17A, IL-17F, IL-22) cytokine as well as cytotoxic (perforin [PFN], granzyme [GZE B], granulysin [GNLSN]) and immune (GMCSF, PD-1, CD69) markers in LTB (DM, PDM, NDM) comorbidities by flow cytometry. In the unstimulated (UNS) condition, we did not observe any significant difference in the frequencies of γδ T cells expressing Th1 and Th17 cytokine, cytotoxic, and immune markers. In contrast, upon PPD antigen stimulation, the frequencies of γδ T cells expressing Th1 (IFNγ, TNFα) and Th17 (IL-17F, IL-22) cytokine, cytotoxic (PFN, GZE B, GNLSN), and immune (CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, upon WCL antigen stimulation, the frequencies of γδ T cells expressing Th1 (TNFα) and Th17 (IL-17A, IL-22) cytokine, cytotoxic (PFN), and immune (PD-1, CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Finally, upon P/I stimulation we did not observe any significant difference in the γδ T cell frequencies expressing cytokine, cytotoxic, and immune markers between the study populations. The culture supernatant levels of IFNγ, TNFα, and IL-17A cytokines were significantly increased in LTB DM and PDM after stimulation with Mtb antigens compared to LTB NDM individuals. Therefore, diminished γδ T cells expressing cytokine, cytotoxic, and other immune markers and elevated levels of cytokines in the supernatants is a characteristic feature of LTB PDM/DM co-morbidities.

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