T helper 17 and regulatory T-cell profile and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients with beta-thalassemia

Bayegi, Shideh Namazi; Hamidieh, Amir Ali; Behfar, Maryam; Saghazadeh, Amene; Bozorgmehr, Mahmood; Karamlou, Yalda; Shekarabi, Mehdi; Tajik, Nader; Delbandi, Ali‐Akbar; Zavareh, Farzaneh Tofighi; Delavari, Samaneh; Rezaei, Nima

doi:10.1016/j.trim.2023.101803

Cited by 2 publications

(1 citation statement)

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“…Immune cell profiling revealed that the reduction in clinical and histological GVHD in humanised mouse by the anti-hP2X7 mAb corresponded to an increase in hTregs and to a lesser extent hNK T cells and hNK cells and a reduction in hTh17 cells, which also corresponded to a decreased hTh17:hTreg ratio. These results largely parallel observations in humans following allogeneic HSCT, where higher proportions of hTregs, hNK T cells, and hNK cells correlate with decreased GVHD severity [ 39 , 40 , 41 ], and where increased proportions of hTh17 cells or higher ratios of hTh17:hTreg correlate with increased GVHD severity [ 42 , 43 ]. Moreover, hTregs and hNK T cells have been shown to reduce GVHD severity in humanised NSG mice [ 44 , 45 ], while hNK cells are required for intravenous immunoglobulin-induced GVHD prevention in these mice [ 46 ].…”

Section: Discussionsupporting

confidence: 73%

A Species-Specific Anti-Human P2X7 Monoclonal Antibody Reduces Graft-versus-Host Disease in Humanised Mice

Elhage,

Cuthbertson,

Sligar

et al. 2023

Pharmaceutics

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Graft-versus-host disease (GVHD) is a T cell-mediated inflammatory disorder that arises from allogeneic haematopoietic stem cell transplantation and is often fatal. The P2X7 receptor is an extracellular adenosine 5′-triphosphate-gated cation channel expressed on immune cells. Blockade of this receptor with small molecule inhibitors impairs GVHD in a humanised mouse model. A species-specific blocking monoclonal antibody (mAb) (clone L4) for human P2X7 is available, affording the opportunity to determine whether donor (human) P2X7 contributes to the development of GVHD in humanised mice. Using flow cytometric assays of human RPMI 8266 and murine J774 cells, this study confirmed that this mAb bound and impaired human P2X7. Furthermore, this mAb prevented the loss of human regulatory T cells (hTregs) and natural killer (hNK) T cells in vitro. NOD-scid IL2Rγnull mice were injected with 10 × 106 human peripheral blood mononuclear cells (Day 0) and an anti-hP2X7 or control mAb (100 μg i.p. per mouse, Days 0, 2, 4, 6, and 8). The anti-hP2X7 mAb increased hTregs and hNK cells at Day 21. Moreover, anti-hP2X7 mAb-treatment reduced clinical and histological GVHD in the liver and lung compared to the control treatment at disease endpoint. hTregs, hNK, and hNK T cell proportions were increased, and human T helper 17 cell proportions were decreased at endpoint. These studies indicate that blockade of human (donor) P2X7 reduces GVHD development in humanised mice, providing the first direct evidence of a role for donor P2X7 in GVHD.

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