The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage.
OBJECTIVE
Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage.


METHODS
Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry.


RESULTS
The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from trauma-hemorrhage animals depressed MHC class II expression of CD11c(+) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage.


CONCLUSIONS
These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage.
Walz
Christian R
CR
Department of Surgery, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.
Zedler
Siegfried
S
Schneider
Christian P
CP
Albertsmeier
Markus
M
Loehe
Florian
F
Bruns
Christiane J
CJ
Faist
Eugen
E
Chaudry
Irshad H
IH
Angele
Martin K
MK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016063:Blood Loss, Surgical / Q000503:physiopathology; D002450:Cell Communication / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D018189:Immunomagnetic Separation; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D016207:Cytokines; D000949:Histocompatibility Antigens Class II