Natural Killer Cells Dominate the Hyperacute Lymphocyte Response to Major Trauma and Are Associated with Organ...

The cellular immune response underlying post-injury multiple organ dysfunction syndrome (MODS) remains incompletely described. We hypothesized that early perturbations in innate lymphocyte behavior are critical to the development of MODS in trauma patients. To address this, we examined lymphocyte subsets in a prospective cohort of major trauma patients recruited at a single major trauma hospital. Circulating lymphocytes were profiled with flow cytometry in serial samples drawn within the hyperacute (≤2 h) and acute (24 h, 72 h) post-injury periods. Plasma levels of specific mediators derived from innate lymphocytes were also measured in a larger cohort. We observed a marked hyperacute increase in circulating NK (particularly the CD56^dim subset) and Vδ1 cells that were associated with MODS or early mortality. Absolute counts of NK activation markers CD69 and NKG2D were also higher in patients with adverse outcomes, although the proportion of NK cells expressing NKG2D was reduced. Exploratory cluster analyses of NK activating and inhibiting receptors identified patient groups with differing injury characteristics and outcomes. In plasma, patients who developed MODS had significantly higher levels of NK-associated cytotoxic mediators and cytokines. Collectively, these data indicate a specific pattern of hyperacute NK cell activation after major trauma that is characterized by a pattern consistent with cytotoxic lymphocyte activation and is associated with clinical outcome.