scholarly journals THE ROLE OF MULTIPARAMETRIC FLOW CYTOMETRY IN DETECTING AND CHARACTERIZING GAMMA‐DELTA T‐CELL ENTITIES IN PERIPHERAL BLOOD. SINGLE‐CENTER CASE SERIES AND LITERATURE REVIEW

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
F Martín Moro ◽  
I Martín Rubio ◽  
R Alonso ◽  
C López ◽  
J Marquet ◽  
...  
2016 ◽  
Vol 16 (2) ◽  
pp. e15-e19 ◽  
Author(s):  
Rakhshandra Talpur ◽  
Ramya Chockalingam ◽  
Casey Wang ◽  
Michael T. Tetzlaff ◽  
Madeleine Duvic

1995 ◽  
Vol 95 (1) ◽  
pp. 296-303 ◽  
Author(s):  
M Takamizawa ◽  
F Fagnoni ◽  
A Mehta-Damani ◽  
A Rivas ◽  
E G Engleman

1993 ◽  
Vol 178 (1) ◽  
pp. 121-127 ◽  
Author(s):  
K Beldjord ◽  
C Beldjord ◽  
E Macintyre ◽  
P Even ◽  
F Sigaux

To characterize the T cell receptor (TCR) repertoire expressed by the V delta 1+ gamma/delta T cell population, we have studied the V delta 1-J delta 1 junctional sequences from peripheral blood samples of healthy donors. We show that, surprisingly, this repertoire is restricted in most healthy adults, with a donor-specific and relatively stable pattern, whereas this repertoire remains unrestricted in infants, and is similar to that of thymocytes. These data contrast with the general assumption that the junctional repertoire of V delta 1+ gamma/delta T cells is extensive, and strongly suggest that peripheral recruitment of V delta 1+ cells bearing particular TCR occurs in humans during the postnatal stage.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A727-A727
Author(s):  
Suresh De Silva ◽  
George Fromm ◽  
Louis Gonzalez ◽  
Arpita Patel ◽  
Kyung Yoon ◽  
...  

BackgroundA primary mechanism of cancer immunotherapy resistance involves downregulation of specific antigens or major histocompatibility complex based antigen presentation, which renders tumor cells invisible to alpha-beta T cells, but not gamma-delta T cells. Recently, a two-step model of gamma-delta T cell activation has emerged, wherein one butyrophilin (BTN, ie. BTN2A1) directly binds the gamma-delta TCR but is only activated if certain molecular patterns (eg. phosphoantigens) facilitate recruitment of a second BTN (ie. BTN3A1) into a complex to form a BTN2A1/3A1 heterodimer. The BTN2A1/3A1 complex specifically activates the predominant gamma-delta T cell population in the peripheral blood, comprising the Vg9d2 T cell receptor (TCR), but does not activate the primary gamma-delta T cell population in mucosal tissues, comprising the Vg4 TCR. The unique mechanism of action and specificity of gamma-delta TCR/BTN interactions suggests that therapeutic proteins comprising specific BTN heterodimers could be used to target specific gamma-delta T cell populations, with a lower risk of off-target activation common with CD3-directed T cell engagers.MethodsHuman BTN2A1/3A1-Fc-CD19scFv and mouse BTNL1/6-Fc-CD19scFv heterodimeric fusion proteins were purified and binding to CD19 or the respective gamma-delta TCRs was assessed by ELISA, Octet and flow cytometry using gd T-cells isolated from human peripheral blood and mouse intestinal tissue. The functionality of the constructs to activate gamma-delta T cells and mediate killing of tumor cells was assessed using live cell imaging in vitro as well as a murine B-cell lymphoma model in vivo.ResultsThe CD19-targeting scFv domains of the BTN heterodimer fusion proteins bound to human and mouse CD19 with low nanomolar affinity. The BTN2A1/3A1-Fc-CD19scFv compound specifically bound to the Vg9d2 TCR on human gd T cells while the mouse BTNL1/6-Fc-CD19scFv bound to Vg7d4 TCR on mouse gd T cells. Both compounds were able to activate gd T cells in a co-culture assay resulting in degranulation and increased surface expression of CD107a and also increased apoptosis of CD19+ tumor cells. Intraperitoneal administration of the mouse BTNL1/6-Fc-CD19scFv led to anti-tumor effects in A20 tumor bearing BALB/c mice. Phenotyping from BTNL1/6-Fc-CD19scFv treated mice revealed profound and rapid expansion of the endogenous gamma-delta T cells in the circulation and tumor, with concomitant depletion of peripheral CD19+ B-cells, confirming the mechanism of action of the heterodimer as a gamma-delta T cell specific engager.ConclusionsThese results provide proof of mechanism for in vivo manipulation of gamma-delta T cells using antigen-targeted butyrophilin heterodimeric fusion proteins for the treatment of cancer.


2021 ◽  
Vol 8 (4) ◽  
pp. 515-524
Author(s):  
Silvia Alberti-Violetti ◽  
Carlo Alberto Maronese ◽  
Luigia Venegoni ◽  
Valentina Merlo ◽  
Emilio Berti

Primary cutaneous gamma-delta T cell lymphomas (PCGDTCLs) are rare and aggressive cutaneous malignancies that have been diagnostically challenging for dermopathologists and clinicians since their first published descriptions in 1991. Since then, the availability of immunostaining for T cell receptors γ and δ in formalin-fixed paraffin-embedded samples has greatly increased our knowledge of the gamma-delta phenotype by showing that it may also be present in the context of indolent entities, such as mycosis fungoides (MFs) and lymphomatoid papulosis, and this has raised questions concerning its diagnostic and prognostic implications. We here describe the histological and clinical differences between the dermo-epidermal and subcutaneous sub-groups of PCGDTCL observed in a cohort of 20 patients attending a single experienced centre, with particular focus on cases with an MF-like presentation, which are still less well defined than those of classic MF.


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