Cold Atmospheric Plasma as an Immunomodulator: Suppression of T-cell Hyperactivation and Graft-versus-Host Disease via Redox Regulation

Cold Atmospheric Plasma (CAP) has garnered significant attention in biomedical science, owing to its wide therapeutic applications in wound healing, disinfection, dentistry, cancer care and inflammation. Although, anti-inflammatory effects of CAP are studied, there are no reports investigating its effect on T cell hyperactivation associated pathologies. This study examines CAP's impact on antigen driven and homeostatic T cell proliferation and its potential to prevent acute graft-versus-host disease (aGvHD). CAP treatment significantly attenuated GvHD-associated mortality and morbidity in mice. CAP inhibited stimulation-induced T cell activation, surface marker expression, cytokine secretion, and proliferation without inducing cell death, indicating non-cytotoxic immunomodulation. CAP modulated cellular redox and pre-treatment with N-acetylcysteine (NAC) or PEG-catalase (PEG-CAT) abrogated CAP-mediated suppression of mitogen-induced T cell responses. Moreover, CAP-mediated inhibition of stimulation-induced T-cell responses was associated with suppression of immune-regulatory, redox-sensitive transcription factors, NF-κB and Nrf2. These findings underscore immunotherapeutic potential of CAP in treatment of disorders linked to T cell hyperactivation.