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 (Injury Severity Score >/= 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 (cluster of differentiation (CD)4, CD8, CD14), cell surface receptor expression (programmed cell death protein 1 (PD-1), B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4, toll-like receptor (TLR)-2, -4, and -5, Dectin-1, programmed death ligand 1 (PD-1L)), and human leucocyte antigen D-related receptor (HLA-DR)-expression were quantified by flow cytometry. Cytokine secretion (IL-2, -4, -6, -10, and 17A, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma) was assessed after stimulation of whole blood with LPS-, alpha-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-alpha secretion showed non-significant trends toward 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 toward an immunosuppressive phenotype. Following major trauma, although IL-6 and TNF-alpha 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=DRKS000 09876.