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Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation

Researchers from the Centre de Recherche Saint-Antoine (CRSA) at Sorbonne Université in France investigated the impact of early recovery of mucosal-associated invariant T (MAIT) cells and gamma-delta (γδ) T cells, particularly the Vδ2⁺ subset, on clinical outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). The authors sought to evaluate the cytotoxicity profile of these cells through the intracellular expression of perforin and granzyme B and the production of IFN-γ after in vitro activation. Overall, early recovery and high frequencies of MAIT and Vδ2⁺CD26⁺ T cells were associated with improved clinical outcomes, including better graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), overall survival (OS), and disease-free survival (DFS), after allo-HCT.

This study was conducted to understand the role of unconventional T cells, such as MAIT and Vδ2⁺ T cells, in influencing clinical outcomes after allo-HCT. The authors aimed to determine if these T cells could provide insights into improving survival rates and reducing complications such as GVHD. Peripheral blood mononuclear cells (PBMC) from 76 patients 20–30 days post-transplant were collected and MAIT cells were identified as CD3⁺ TCRVα7.2⁺CD161⁺. Two subsets of Vδ2⁺ T cells were distinguished based on CD26 expression. Patients with higher MAIT cell frequencies exhibited better GRFS (p = 0.0026), OS (p = 0.015), and DFS (p = 0.0036). Additionally, low CD69 expression in MAIT cells was associated with a higher cumulative incidence of grade 2–4 acute GvHD (aGVHD) (p = 0.04).

For γδ T cells, these findings demonstrate the importance of the Vδ2⁺ subset, particularly those expressing CD26. Vδ2⁺CD26⁺ T cells exhibited higher intracellular levels of IFN-γ, while Vδ2⁺CD26^- T cells were more cytotoxic, expressing higher levels of perforin and granzyme B. Overall, the study indicates that early recovery and the functional status of MAIT and Vδ2⁺ T cells, particularly the CD26⁺ subset, play a crucial role in determining clinical outcomes after allo-HCT. These findings provide a potential avenue for improving post-transplant outcomes by targeting the reconstitution and activation of these unconventional T cells.

Reference:

Siblany L, Stocker N, Ricard L, et al. Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation. J Clin Immunol. 2024;44(6):139. Published 2024 Jun 1.

https://doi.org/10.1007/s10875-024-01741-6