gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Injury rapidly induces TCR-mediated signaling responses in CD4+ T-regs but not in non-T-regs

Meeting Abstract

  • Marc Hanschen - Klinikum der Universitaet Muenchen, Chirurgische Klinik und Poliklinik - Innenstadt, Muenchen
  • Goro Tajima - Brigham and Women's Hospital / Harvard Medical School, Department of Surgery (Immunology), Boston
  • Fionnuala O'Leary - Brigham and Women's Hospital / Harvard Medical School, Department of Surgery (Immunology), Boston
  • Kimiko Ikeda - Brigham and Women's Hospital / Harvard Medical School, Department of Surgery (Immunology), Boston
  • James Lederer - Brigham and Women's Hospital / Harvard Medical School, Department of Surgery (Immunology), Boston

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch813

DOI: 10.3205/11dgch813, URN: urn:nbn:de:0183-11dgch8139

Veröffentlicht: 20. Mai 2011

© 2011 Hanschen et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Severe injury enhances the regulatory activity of CD4+ T regulatory cells (Tregs), but the mechanisms responsible for Treg activation following injury remain unclear. Objectives of this study were (i) to test whether injury differentially activates T cell receptor (TCR) signaling in CD4+ Treg and non-Treg cells and (ii) to investigate whether Treg activation following injury is TCR dependent.

Materials and methods: We employed phospho-flow cytometry rather than Western immunoblots to measure the phosphorylation of the TCR signaling molecules, ZAP-70, PKC-theta, NFATc1, and GSK-3beta in FoxP3+ Tregs and non-Tregs. In a first set of experiments, C57BL/6 mice were subjected to 25% total body surface burn injury or sham treated and lymph nodes (LN) and spleens (SPL) were harvested to measure signaling activation at early time points – 15, 30, 60, 120, and 240 minutes – after sham or burn injury. In a second set of experiments, the TCR-dependency of signaling activation following injury was investigated using mice with a highly restricted TCR repertoire (OT-II TCR transgenic mice). Following burn or sham injury, the expression and phosphorylation of TCR signaling molecules was analyzed in Tregs vs. non-Tregs derived from wild-type or OT-II mice.

Results: Burn injury induced a significant differential signaling response in Tregs vs. non-Tregs derived from the LN of WT mice as early as 15 min after injury. This effect could not be observed in Tregs derived from SPL. Non-Tregs did not show an early signaling response to burn injury. In contrast to WT Tregs, no rapid signaling activation was detectable in OT-II Tregs, indicating a potential role for the TCR in Treg activation following injury.

Conclusion: In conclusion, we show that injury induces differential signaling by Tregs and non-Tregs and provide evidence to indicate that burn injury preferentially activates TCR signaling by Tregs in the LNs draining the injury site.