Adoptively Transferred in vitro-Generated Myeloid-Derived Suppressor Cells Improve T-Cell Function and Antigen-Specific Immunity after Traumatic Lung Injury

Immune reactions after trauma are characterized by immediate activation of innate immunity and simultaneously downregulation of adaptive immunity leading to a misbalanced immunohomeostasis and immunosuppression of the injured host. Therefore, the susceptibility to secondary infections is strongly increased after trauma. Immune responses are regulated by a network of immune cells influencing each other and at the same time modifying their functions dependent on the inflammatory environment. Although myeloid-derived suppressor cells (MDSCs) are initially described as T-cell suppressors, their immunomodulatory capacity after trauma is mostly undefined. Therefore, in vitro-generated MDSCs were adoptively transferred into mice after blunt chest trauma (TxT). A single MDSC treatment-induced splenic T-cell expansion decreased apoptosis sensitivity and improved proliferation in the absence of T-cell exhaustion until 2 weeks after trauma. MDSC treatment had a long-lasting effect on the genomic landscape of CD4(+) T cells by upregulating primarily Th2-associated genes. Remarkably, immune-activating functions of MDSCs supported the ability of TxT mice to respond to post-traumatic secondary antigen challenge. Secondary insults were mimicked by immunizing MDSC-treated TxT mice with ovalbumin (OVA), followed by OVA restimulation in vitro. MDSC treatment significantly increased the frequency of OVA-specific T cells, enhanced their Th1/Th2 cytokine expression, and induced upregulation of cytolytic molecules finally improving OVA-specific cytotoxicity. Overall, we could show that therapeutic MDSC treatment after TxT improves post- traumatic T-cell functions, which might enable the traumatic host to counterbalance trauma-induced immunoparalysis. (c) 2022 The Author(s). Published by S. Karger AG, Basel

Automated summary

Immune reactions after trauma lead to an imbalanced immunohomeostasis and immunosuppression, increasing susceptibility to secondary infections. The immunomodulatory capacity of myeloid-derived suppressor cells (MDSCs) after trauma is not well-defined. However, studies have shown that therapeutic MDSC treatment can improve post-traumatic T-cell functions and enhance the ability to respond to secondary antigen challenges.