Antioxidant activity of 2-mercaptoethanol protects against CD8+ T cell overstimulation or accelerated exhaustion: evidence from an in vitro exhausted CD8+ T model and in vivo adoptive cell transfer.

作者：Muhammad Alaa Eldeen, Dalal. S. Alshaya, Waleed K. Abdulsahib, Nuha Almulla, Mohamed Ali, Maha A. Aljumaa, E. Fayad, Jawaher Alharthi, Hassan M. Otifi, Mohamed Alshehri, Reem S. Alazragi, Hesham M. Hassan · 发表于：International Immunopharmacology · 年份：2026 · DOI：10.1016/j.intimp.2026.116183 · 被引用次数：1 · 研究领域：Medicine

BACKGROUND CD8+ T cell exhaustion in the tumor microenvironment acts as a barrier to tumor immunotherapy development. Therefore, studying that cell in vitro and in vivo is essential for developing a successful cancer immunotherapeutic drug. METHODS While repeated stimulation of CD8+ T cells in vitro is a must to acquire their exhaustion state, it is important to keep that to a limit that allows for exhaustion of the CD8+ T cells without accelerated cell death, so we can obtain enough exhausted CD8+ T cells to be studied. In the current study, we demonstrated the role of 2-mercaptoethanol (2-ME) as an essential media component by performing repeated CD8+ T cell stimulation with or without 2-ME. RESULTS In the absence of 2-ME, CD8+ T cell suffers from overstimulation that allows for their accelerated death. Mechanistically, the absence of 2-ME elevates the oxidative stress on the CD8+ T cells, leading to a shift in their metabolic pathways by adopting lipid peroxidation, which hastens CD8+ T cells' terminal differentiation and over-activates the AKT-mTOR signaling pathway, and finally, cell death. These findings were reflected in our in vivo experiment, where adoptive transfer of antigen-specific CD8+ T cells that have been in vitro activated without 2-ME experienced a lower tumor infiltration frequency and diminished stemness characteristics and effector functions. CONCLUSION Our study confirms the importance of 2-ME as a media component for CD8+ T cells stimulation and ...