scholarly journals αβ T cells replacing dermal and epidermal γδ T cells in Tcrd –/– mice express an MHC‐independent TCR repertoire

2021 ◽  
Author(s):  
Christoph Binz ◽  
Anja Bubke ◽  
Inga Sandrock ◽  
Immo Prinz
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Tcr Repertoire ◽  
Αβ T Cells

scholarly journals Human γδ TCR Repertoires in Health and Disease

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 800 ◽  
Author(s):  
Alina Suzann Fichtner ◽  
Sarina Ravens ◽  
Immo Prinz
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Γδ T Cell ◽  
Tcr Repertoire ◽  
Repertoire Diversity ◽  
Health And Disease ◽  
Αβ T Cells

The T cell receptor (TCR) repertoires of γδ T cells are very different to those of αβ T cells. While the theoretical TCR repertoire diversity of γδ T cells is estimated to exceed the diversity of αβ T cells by far, γδ T cells are still understood as more invariant T cells that only use a limited set of γδ TCRs. Most of our current knowledge of human γδ T cell receptor diversity builds on specific monoclonal antibodies that discriminate between the two major subsets, namely Vδ2+ and Vδ1+ T cells. Of those two subsets, Vδ2+ T cells seem to better fit into a role of innate T cells with semi-invariant TCR usage, as compared to an adaptive-like biology of some Vδ1+ subsets. Yet, this distinction into innate-like Vδ2+ and adaptive-like Vδ1+ γδ T cells does not quite recapitulate the full diversity of γδ T cell subsets, ligands and interaction modes. Here, we review how the recent introduction of high-throughput TCR repertoire sequencing has boosted our knowledge of γδ T cell repertoire diversity beyond Vδ2+ and Vδ1+ T cells. We discuss the current understanding of clonal composition and the dynamics of human γδ TCR repertoires in health and disease.

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 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.

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