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December 8, 2025BloodOpen Access

Monocarboxylate transporter 1 deficient donor T cells rewire metabolism and ameliorate aGVHD lethality

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Authors

ASAsim SahaCMCameron McDonald-HymanJRJeffrey C. Rathmell

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Overview

MCT1 deletion reduces aGVHD lethality in T cells, suggesting a novel therapeutic strategy for treatment.

Key Points

  • This research examines the impact of MCT1 deletion in donor T cells on aGVHD outcomes.
  • Used donor T cell-specific MCT1 knockout mice and lethally irradiated MHC-mismatched recipients.
  • Evaluated survival, weight loss, T cell phenotype, and organ infiltration in aGVHD models.
  • Performed in vitro metabolic profiling of MCT1 KO T cells using advanced techniques such as flow cytometry and mass spectrometry.
  • MCT1 KO T cells exhibited 30% reduced proliferation and diminished extracellular acidification.
  • MCT1 KO recipients showed aGVHD lethality at 70% compared to 0% in WT recipients (p<0.0001).
  • Increased Treg (CD25+Foxp3+) to T cell ratio in MCT1 KO recipients, indicating enhanced regulatory function.

Cite This Study

Saha et al. (2025) studied this question.

synapsesocial.com/papers/69362f484fa91c937236d6e4https://doi.org/10.1182/blood-2025-5867
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