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

Abstract

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. 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)-α, and interferon (IFN)-γ) was assessed after stimulation of whole blood with LPS-, α-CD3/28, or zymosan. 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 toward reduced values. No differences regarding clinical apparent infections could be detected. 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-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. 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.