Circulating Factors in Trauma Plasma Activate Specific Human Immune Cell Subsets.

Area of Science:

• Immunology
• Trauma Research
• Cellular Biology

Background:

• Trauma triggers release of damage-associated molecular patterns (DAMPs) and mediators, disrupting immune homeostasis.
• These disruptions can lead to severe complications like infections and sepsis.
• Understanding trauma-induced immune alterations is crucial for identifying therapeutic targets.

Purpose of the Study:

• To characterize how trauma plasma affects peripheral blood mononuclear cell (PBMC) activation.
• To investigate the kinetics and nature of trauma-induced circulating factors on human immune cells.
• To gain insights into immune cell responses for potential therapeutic development in acute trauma.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with healthy or trauma plasma (1-day or 3-day post-trauma).
• Time-of-flight mass cytometry (CyTOF) was used with a comprehensive antibody panel for immunophenotyping.
• Multiplex (Luminex) assays measured cytokine levels in plasma samples.

Main Results:

• Day 1 trauma plasma induced acute expansion of CD11c+ NK cells and CD73+/CCR7+ CD8 T cell subpopulations.
• Trauma plasma caused a phenotypic shift in CD4+ T cells towards CD38+/CCR7+ expression, without expansion.
• Elevated IL-1RA, IL-6, and IL-15 levels were detected in day 1 trauma plasma.

Conclusions:

• Circulating factors in trauma plasma induce significant phenotypic changes in normal human immune cell subsets.
• CD11c+ NK cells expanded in response to trauma plasma, similar to their response to DAMPs and LPS.
• The study identifies specific NK and CD8+ T cell subset changes in response to trauma plasma, highlighting their role in acute traumatic injury.