gms | German Medical Science

Objectives: Major trauma patients who initially survive their injury are at risk for profound immune suppression in their clinical course. Immune suppressive conditions facilitate development of infectious complications in the later post-injury phase. Regulatory T cells (Tregs) are potent suppressors of the immune response. Previously, we have demonstrated profound changes in peripheral Tregs after trauma. However, despite their decreased numbers in peripheral blood, after a secondary ex vivo in vitro stimulation, they demonstrate an increase in their potency (induction) in the later post-injury phase. Due to these intriguing data, here, we evaluated the activity of Tregs, and the underlying mechanism for their malfunction after major trauma.

Methods: Twenty-two patients with major trauma (TP, ISS 30±2) and 18 healthy volunteers (HV) were enrolled. Peripheral blood was withdrawn from the admittance to the emergency department (ED) and on following days 1 to 10 daily after trauma. The numbers of CD4⁺CD25^high and CD4⁺CD25⁺CD127^- Tregs immediately after blood withdrawal or after their ex vivo in vitro stimulation were determined by flow cytometry. The proliferative capacity of isolated T cells by CD3CD28 stimulation, either before or after depletion of CD4⁺CD25⁺CD127^- Tregs by MACS separation, was assessed in samples obtained at ED. Additionally, the functional role of IL-10 for Tregs-mediated T cell proliferation was analysed by using neutralizing IL-10 or IL-10 receptor antibodies.

Results: CD4⁺CD25^high and CD4⁺CD25⁺CD127^- Tregs were significantly decreased in peripheral blood lymphocytes during the ten days post-injury phase compared to HV. In contrast, their ex vivo in vitro induction increased continuously during the time course. Depletion of CD4⁺CD25⁺CD127^- Tregs increased significantly the T cell proliferative capacity in HV. Additional neutralizing of IL-10 by both, anti-IL-10 and anti-IL-10R antibodies increased further the T cell proliferation in HV. Depletion of Tregs from the T cell population isolated from TP at ED decreased the CD3CD28 induced proliferation. While additional neutralization by anti-IL-10 antibody decreased further the T cell proliferation in TP, anti-IL-10R antibody did not have significant influence.

Conclusion: Our data show that despite their lower numbers in peripheral blood, Tregs demonstrate increased induction in the later post-injury phase. Regarding their functional activity, under healthy conditions, Tregs exert their immune-suppressive effects on T cell proliferation via IL-10 and the corresponding IL-10 receptor. In contrast, immediately after trauma, Tregs are suppressed in their T cell proliferation-reducing capacity. While the underlying mechanism involves IL-10, the IL-10R does not play the same role in TP as it was demonstrated under healthy conditions.