Adoptively Transferred in vitro-Generated Myeloid-Derived Suppressor Cells Improve T-Cell Function and...

Area of Science:

• Immunology
• Trauma Research
• Cell Therapy

Background:

• Trauma triggers innate immunity activation and adaptive immunity suppression, increasing infection susceptibility.
• The role of myeloid-derived suppressor cells (MDSCs) in post-trauma immune modulation remains unclear.
• Trauma-induced immunosuppression, or immunoparalysis, impairs the host's ability to fight secondary infections.

Purpose of the Study:

• To investigate the immunomodulatory effects of adoptively transferred myeloid-derived suppressor cells (MDSCs) in a mouse model of blunt chest trauma (TxT).
• To assess the impact of MDSC treatment on T-cell function, genomic landscape, and response to secondary antigen challenge post-trauma.

Main Methods:

• In vitro-generated MDSCs were adoptively transferred into mice following blunt chest trauma (TxT).
• Assessed splenic T-cell expansion, apoptosis sensitivity, proliferation, and T-cell exhaustion markers up to 2 weeks post-trauma.
• Analyzed genomic changes in CD4+ T cells and evaluated immune response to secondary ovalbumin (OVA) challenge.

Main Results:

• Single MDSC treatment promoted splenic T-cell expansion, reduced apoptosis, and enhanced proliferation without T-cell exhaustion.
• MDSC treatment led to sustained upregulation of Th2-associated genes in CD4+ T cells.
• MDSC-treated mice showed improved response to secondary OVA challenge, with increased OVA-specific T cells, enhanced cytokine expression, and improved cytotoxicity.

Conclusions:

• Therapeutic MDSC administration post-trauma effectively restores and enhances T-cell functions.
• MDSC treatment counteracts trauma-induced immunoparalysis, improving the host's ability to respond to secondary infections.
• MDSC-based cell therapy holds promise for managing post-traumatic immunosuppression and reducing infection risk.