eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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3/2021
vol. 46
 
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abstract:
Experimental immunology

The posttraumatic response of CD4+ regulatory T cells is modulated by direct cell-cell contact via CD40L- and P-selectin-dependent pathways

Marco-Christopher Rupp
1
,
Christian Benjamin Bergmann
1
,
Sonja Jung
1
,
Matthias Bock
1
,
Peter Biberthaler
1
,
Laura Heimann
1
,
Marc Hanschen
1

  1. Experimental Trauma Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
Cent J Eur Immunol 2021; 46 (3): 283-294
Online publish date: 2021/10/19
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CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC- and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-: p < 0.05, pPKC-: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-: p = 0.68, pPKC-: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-: p = 0.81, pPKC-: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.
keywords:

CD4+ regulatory T cells, platelets, trauma, adaptive immune response, hemostasis, cell communication

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