Artikel
Significant decline of CD4+CD25+, CD4+CD25+CD127- and CD4+CD25+FOXP3+ regulatory T cell subsets and their increased induction after major trauma
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Veröffentlicht: | 5. Oktober 2015 |
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Gliederung
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Background: Regulatory T cells (Tregs) represent important and potent suppressors of immune responses. Multiply traumatized patients who survive the initial trauma are at risk for profound immune suppression that may facilitate infectious complications in the later post-injury phase. Different subsets of Tregs have been described, however there is a large lack of knowledge about their presence, distribution and induction following trauma. We describe phenotypically distinct populations of Tregs and their diverse systemic induction after major trauma.
Material/Methods: Twenty patients with major trauma (ISS: 29 ± 3) and fifteen healthy volunteers as controls (ctrl) were enrolled. Peripheral blood was withdrawn from the admittance to the emergency department (ED) and on following days 1 to 10 daily after trauma. CD4+CD25+, CD4+CD25+CD127- and CD4+CD25+FOXP3+ Tregs were identified by flow cytometry and their percentage inductiveness with the Leukocyte Activation Cocktail (LAC) was assessed.
Results: Significantly decreased percentages of all three Tregs subsets in peripheral blood lymphocytes were observed at the admission compared to ctrl. The Tregs remained at lower cell numbers during the ten days post-injury phase. LAC-induction of CD4+CD25+, CD4+CD25+CD127- or CD4+CD25+FOXP3+ Tregs was initially (ED) lower compared to ctrl. The inductiveness of Tregs in samples from trauma patients increased continuously during the time course. The induction of CD4+CD25+/Low Tregs was not significant during the time course. However, induction of CD4+CD25+/High was steadily increased after day 6 compared to ctrl. Compared to ctrl, the persistent and significant increase of the CD4+CD25+CD127- and CD4+CD25+FOXP3+ phenotype induction by LAC began after day 6 and persisted until day 10 in samples from trauma patients.
Conclusion: Our data demonstrate that major trauma is followed by profound changes in peripheral Tregs subsets. Despite their decreased numbers in peripheral blood they demonstrate an increase in their potency in the later post-injury phase beginning at day 6. Considering that infectious complications occur during this later post-injury phase, the increased Tregs responses may contribute to immune-suppression and thereby increased immunological alteration. The relevance of delayed Tregs induction for infectious complications after major trauma has to be evaluated in further studies.