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Inflammation-induced epigenetic imprinting regulates intestinal stem cells

Researchers from Bambino Gesù Children’s Hospital and Sapienza University in Rome, Italy examined the recovery and function of mucosal-associated invariant T (MAIT) cells in pediatric and young adult patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). MAIT cells are critical for responding to bacterial and fungal infections, but their role in post-transplant immune reconstitution and clinical outcomes remains poorly understood. This retrospective study included 145 patients treated between 2019 and 2022, receiving either matched unrelated donor (MUD) or HLA-haploidentical (Haplo) HSCT with αβT/CD19-cell depletion. Despite successful αβT-cell reconstitution within two years post-transplant, MAIT cells showed delayed recovery, prolonged functional impairment, and significant expression of activation (CD25, CD38), exhaustion (PD1, TIM3), and senescence (CD57) markers.

The researchers found that higher MAIT-cell levels at day 30 post-transplant were associated with increased incidences of grade II-IV acute graft-versus-host disease (aGvHD) and chronic GvHD (cGvHD). Additionally, early MAIT-cell recovery correlated with a higher risk of cytomegalovirus (CMV) reactivation but lower rates of late bloodstream infections (BSI). Interestingly, MAIT cells showed a suboptimal response to microbial and T-cell receptor stimulation in vitro, indicating a dysfunctional state. These findings underscore the complex role of MAIT cells in post-HSCT immune reconstitution, suggesting that their early presence may have both beneficial and detrimental effects depending on the clinical context.

This study highlights the need for further research to understand the mechanisms underlying MAIT-cell recovery and its impact on allo-HSCT outcomes. Targeting MAIT-cell reconstitution through strategies that optimize their function while mitigating adverse effects like GvHD could improve post-transplant outcomes. The authors emphasize the importance of investigating the interplay between MAIT cells, microbiota, and thymic function in this setting.

Reference:

Galaverna F, Flamini S, De Luca CD, et al. Mucosal-associated invariant T cells are functionally impaired in pediatric and young adult patients following allogeneic hematopoietic stem cell transplantation and their recovery correlates with clinical outcomes. Haematologica. 2024;109(10):3222-3236. Published 2024 Oct 1. http://doi.org/10.3324/haematol.2023.284649