scholarly journals Unlike αβ T cells, γδ T cells, LTi cells and NKT cells do not require IRF4 for the production of IL-17A and IL-22

2012 ◽  
Vol 42 (12) ◽  
pp. 3189-3201 ◽  
Author(s):  
Hartmann Raifer ◽  
Azita J. Mahiny ◽  
Nadine Bollig ◽  
Franziska Petermann ◽  
Anne Hellhund ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Nkt Cells ◽  
Αβ T Cells

scholarly journals The molecular bases of δ/αβ T cell–mediated antigen recognition

2014 ◽  
Vol 211 (13) ◽  
pp. 2599-2615 ◽  
Author(s):  
Daniel G. Pellicci ◽  
Adam P. Uldrich ◽  
Jérôme Le Nours ◽  
Fiona Ross ◽  
Eric Chabrol ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Biology ◽  
Γδ T Cells ◽  
Nkt Cells ◽  
Type I ◽  
Human Immune System ◽  
Human T Cells ◽  
Molecular Bases ◽  
Αβ T Cells

αβ and γδ T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the αβ and γδ T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term δ/αβ T cells, expressing TCRs comprised of a TCR-δ variable gene (Vδ1) fused to joining α and constant α domains, paired with an array of TCR-β chains. We demonstrate that these cells, which represent ∼50% of all Vδ1+ human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive δ/αβ T cells recognized α-galactosylceramide (α-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as α-glucosylceramide, was distinct from type I NKT cells. Thus, δ/αβTCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how δ/αβTCRs bind to their targets, with the Vδ1-encoded region providing a major contribution to δ/αβTCR binding. Our findings highlight how components from αβ and γδTCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity.

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells

scholarly journals Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury

2009 ◽  
Vol 296 (5) ◽  
pp. G1054-G1059 ◽  
Author(s):  
Satoshi Kuboki ◽  
Nozomu Sakai ◽  
Johannes Tschöp ◽  
Michael J. Edwards ◽  
Alex B. Lentsch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Nkt Cells ◽  
T Cell Subsets ◽  
Wild Type ◽  
Hepatic Ischemia ◽  
Hepatic Ischemia Reperfusion

Helper T cells are known to mediate hepatic ischemia/reperfusion (I/R) injury. However, the precise mechanisms and subsets of CD4+ T cells that contribute to this injury are still controversial. Therefore, we sought to determine the contributions of different CD4+ T cell subsets during hepatic I/R injury. Wild-type, OT-II, or T cell receptor (TCR)-δ-deficient mice were subjected to 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Additionally, wild-type mice were pretreated with anti-CD1d, -NK1.1, or -IL-2R-α antibodies before I/R injury. OT-II mice had diminished liver injury compared with wild-type mice, implicating that antigen-dependent activation of CD4+ T cells through TCRs is involved in hepatic I/R injury. TCR-δ knockout mice had decreased hepatic neutrophil accumulation, suggesting that γδ T cells regulate neutrophil recruitment. We found that natural killer T (NKT) cells, but not NK cells, contribute to hepatic I/R injury via CD1d-dependent activation of their TCRs, as depletion of NKT cells by anti-CD1d antibody or depletion of both NKT cells and NK cells by anti-NK1.1 attenuated liver injury. Although regulatory T cells (Treg) are known to suppress T cell-dependent inflammation, depletion of Treg cells had little effect on hepatic I/R injury. The data suggest that antigen-dependent activation of CD4+ T cells contributes to hepatic I/R injury. Among the subsets of CD4+ T cells, it appears that γδ T cells contribute to neutrophil recruitment and that NKT cells directly injure the liver. In contrast, NK cells and Treg have little effects on hepatic I/R injury.

scholarly journals γδ T cells present antigen to CD4+ αβ T cells

1998 ◽  
Vol 63 (6) ◽  
pp. 707-714 ◽  
Author(s):  
Robert A. Collins ◽  
Dirk Werling ◽  
Sara E. Duggan ◽  
A. Patricia Bland ◽  
Keith R. Parsons ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Αβ T Cells

scholarly journals αβ-T Cells Engineered to Express γδ-T Cell Receptors Can Kill Neuroblastoma Organoids Independent of MHC-I Expression

2021 ◽  
Vol 11 (9) ◽  
pp. 923
Author(s):  
Josephine G. M. Strijker ◽  
Ronja Pscheid ◽  
Esther Drent ◽  
Jessica J. F. van der Hoek ◽  
Bianca Koopmans ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transcriptional Profiling ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Target Cells ◽  
Γδ T Cell ◽  
Mhc I ◽  
Organization Analysis ◽  
Αβ T Cells

Currently ~50% of patients with a diagnosis of high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression of neuroblastoma represents a major challenge for T cell-mediated immunotherapy. Here, we propose a novel T cell-based immunotherapy approach for neuroblastoma, based on the use of TEG002, αβ-T cells engineered to express a defined γδ-T cell receptor, which can recognize and kill target cells independent of MHC-I. In a co-culture killing assay, we showed that 3 out of 6 neuroblastoma organoids could activate TEG002 as measured by IFNγ production. Transcriptional profiling showed this effect correlates with an increased activity of processes involved in interferon signaling and extracellular matrix organization. Analysis of the dynamics of organoid killing by TEG002 over time confirmed that organoids which induced TEG002 activation were efficiently killed independent of their MHC-I expression. Of note, efficacy of TEG002 treatment was superior to donor-matched untransduced αβ-T cells or endogenous γδ-T cells. Our data suggest that TEG002 may be a promising novel treatment option for a subset of neuroblastoma patients.

scholarly journals An innate-like Vδ1+ γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer

2019 ◽  
Vol 11 (513) ◽  
pp. eaax9364 ◽  
Author(s):  
Yin Wu ◽  
Fernanda Kyle-Cezar ◽  
Richard T. Woolf ◽  
Cristina Naceur-Lombardelli ◽  
Julie Owen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Γδ T Cells ◽  
Γδ T Cell ◽  
Human Breast ◽  
Cell Compartment ◽  
Αβ T Cells

Innate-like tissue-resident γδ T cell compartments capable of protecting against carcinogenesis are well established in mice. Conversely, the degree to which they exist in humans, their potential properties, and their contributions to host benefit are mostly unresolved. Here, we demonstrate that healthy human breast harbors a distinct γδ T cell compartment, primarily expressing T cell receptor (TCR) Vδ1 chains, by comparison to Vδ2 chains that predominate in peripheral blood. Breast-resident Vδ1+ cells were functionally skewed toward cytolysis and IFN-γ production, but not IL-17, which has been linked with inflammatory pathologies. Breast-resident Vδ1+ cells could be activated innately via the NKG2D receptor, whereas neighboring CD8+ αβ T cells required TCR signaling. A comparable population of Vδ1+ cells was found in human breast tumors, and when paired tumor and nonmalignant samples from 11 patients with triple-negative breast cancer were analyzed, progression-free and overall survival correlated with Vδ1+ cell representation, but not with either total γδ T cells or Vδ2+ T cells. As expected, progression-free survival also correlated with αβ TCRs. However, whereas in most cases TCRαβ repertoires focused, typical of antigen-specific responses, this was not observed for Vδ1+ cells, consistent with their innate-like responsiveness. Thus, maximal patient benefit may accrue from the collaboration of innate-like responses mounted by tissue-resident Vδ1+ compartments and adaptive responses mounted by αβ T cells.

Ex vivo-expanded natural killer cells kill cancer cells more effectively than ex vivo-expanded γδ T cells or αβ T cells

2014 ◽  
Vol 22 (2) ◽  
pp. 486-491 ◽  
Author(s):  
Xuewen Deng ◽  
Hiroshi Terunuma ◽  
Atsushi Terunuma ◽  
Tsubasa Takane ◽  
Mie Nieda
Keyword(s):  
T Cells ◽  
Natural Killer Cells ◽  
Cancer Cells ◽  
Natural Killer ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Killer Cells ◽  
Αβ T Cells

scholarly journals Mycobacterium-Specific γ9δ2T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity

2015 ◽  
Vol 84 (2) ◽  
pp. 580-589 ◽  
Author(s):  
Getahun Abate ◽  
Charles T. Spencer ◽  
Fahreta Hamzabegovic ◽  
Azra Blazevic ◽  
Mei Xia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Γδ T Cells ◽  
Cd40 Ligand ◽  
Cell Contact ◽  
Protective Effects ◽  
Inhibitory Effects ◽  
Content Type ◽  
T Cell Lines ◽  
Αβ T Cells

Numerous pathogens, includingMycobacterium tuberculosis, can activate human γ9δ2T cells to proliferate and express effector mechanisms. γ9δ2T cells can directly inhibit the growth of intracellular mycobacteria and may also act as antigen-presenting cells (APC). Despite evidence for γδ T cells having the capacity to function as APC, the mechanisms involved and importance of these effects on overall tuberculosis (TB) immunity are unknown. We preparedM. tuberculosis-specific γ9δ2T cell lines to study their direct protective effects and APC functions forM. tuberculosis-specific αβ T cells. The direct inhibitory effects on intracellular mycobacteria were measured, and the enhancing effects on proliferative and effector responses of αβ T cells assessed. Furthermore, the importance of cell-to-cell contact and soluble products for γ9δ2T cell effector responses and APC functions were investigated. We demonstrate, in addition to direct inhibitory effects on intracellular mycobacteria, the following: (i) γ9δ2T cells enhance the expansion ofM. tuberculosis-specific αβ T cells and increase the ability of αβ T cells to inhibit intracellular mycobacteria; (ii) although soluble mediators are critical for the direct inhibitory effects of γ9δ2T cells, their APC functions do not require soluble mediators; (iii) the APC functions of γ9δ2T cells involve cell-to-cell contact that is dependent on CD40-CD40 ligand (CD40L) interactions; and (iv) fully activated CD4+αβ T cells and γ9δ2T cells provide similar immune enhancing/APC functions forM. tuberculosis-specific T cells. These effector and helper effects of γ9δ2T cells further indicate that these T cells should be considered important new targets for new TB vaccines.

scholarly journals Itch−/−αβ and γδ T cells independently contribute to autoimmunity in Itchy mice

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4273-7282 ◽  
Author(s):  
Valentino Parravicini ◽  
Anne-Christine Field ◽  
Peter D. Tomlinson ◽  
M. Albert Basson ◽  
Rose Zamoyska
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Microbial Pathogens ◽  
Interleukin 4 ◽  
Cell Subpopulation ◽  
Inflammatory Condition ◽  
Independent Manner ◽  
Autoimmune Pathology ◽  
Inflammatory Phenotype ◽  
Αβ T Cells

Abstract E3 ubiquitin ligases determine which intracellular proteins are targets of the ubiquitin conjugation pathway and thus play a key role in determining the half-life, subcellular localization and/or activation status of their target proteins. Itchy mice lack the E3 ligase, Itch, and show dysregulation of T lymphocytes and the induction of a lethal autoimmune inflammatory condition. Itch is widely expressed in hematopoietic and nonhematopoietic cells, and we demonstrate that disease is transferred exclusively by hematopoietic cells. Moreover, distinct manifestations of the autoimmune inflammatory phenotype are contributed by discrete populations of lymphocytes. The presence of Itch-deficient αβ T cells drives expansion of peritoneal B1b cells and elevated IgM levels, which correlate with itching and pathology. In contrast, Itch−/− interleukin-4–producing γδ T cells, even in the absence of αβ T cells, are associated with elevated levels of IgE and an inflammatory condition. These data indicate that disruption of an E3 ubiquitin ligase in αβ T cells can subvert a B-cell subpopulation, which normally functions to control particular microbial pathogens in a T-independent manner, to contribute to autoimmunity. In addition, disruption of Itch in innate γδ T cells can influence autoimmune pathology and might therefore require distinct therapeutic intervention.

Sign in / Sign up

Export Citation Format

Share Document