Trauma-Induced Long-Term Alterations of Human T Cells and Monocytes-Results of an Explorative, Cross-Sectional Study.

BACKGROUND: Major trauma leads to complex immune reactions, known to result in a transient immunodeficiency. The long-term consequences of severe trauma on immune function and regulation as well as its clinical impact remain unclear.

METHODS: Six months (ranging from -12 to +5 days) after a major trauma event, 12 former trauma patients (ISS ≥ 16) and 12 healthy volunteers were enrolled. The current clinical status and infection history since discharge were assessed by a standardized questionnaire. Immune cell subsets (CD4, CD8, CD14), cell surface receptor expression (PD-1, BTLA, CTLA-4, TLR-2, -4, and -5, Dectin-1, PD-1L) and HLA-DR-expression were quantified by flow cytometry. Cytokine secretion (IL-2, -4, -6, -10, and 17A, TNF-α, and IFN-γ) was assessed after stimulation of whole blood with LPS-, α-CD3/28, or zymosan.

RESULTS: Analysis of surface receptors on T cells revealed a significant elevation of PD-1 expression on CD4 T cells, whereas BTLA expression on CD4 and CD8 T cells was significantly suppressed in the trauma cohort. Monocytes showed a significantly reduced expression of TLR-2 and -4 as well as a reduced proportion of TLR-4 monocytes. HLA-DR receptor density revealed no significant changes between both cohorts. LPS-induced IL-6 and TNF-α secretion showed non-significant trends towards reduced values. No differences regarding clinical apparent infections could be detected.

CONCLUSIONS: Six months following major trauma, changes of cell surface receptors on CD4 and CD8 T cells as well as on CD14 monocytes were present, hinting towards an immunosuppressive phenotype. Following major trauma, although IL-6 and TNF-α release after stimulation were reduced, they did not reach statistical significance. Overall, further studies are necessary to evaluate the clinical implications of these findings.

TRIAL REGISTRATION: DRKS00009876, Internet Portal of the German Clinical Trials Register (DRKS), registration date 11.08.2016, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00009876.