The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage.

Abstract

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.

DESIGN:

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.

• Authors: Christian R Walz, Siegfried Zedler, Christian P Schneider, Markus Albertsmeier, Florian Loehe, Christiane J Bruns, Eugen Faist, Irshad H Chaudry, Martin K Angele
• Journal: Innate immunity (Innate Immun) Vol. 15 Issue 4 Pg. 233-41 (Aug 2009) ISSN: 1753-4267 [Electronic] United States
• PMID: 19586998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Cytokines
• Histocompatibility Antigens Class II

Topics

• Animals
• Antigen-Presenting Cells (immunology, metabolism, pathology)
• Antigens, CD (biosynthesis, genetics, immunology)
• Blood Loss, Surgical (physiopathology)
• Cell Communication (immunology)
• Coculture Techniques
• Cytokines (biosynthesis, genetics, metabolism)
• Flow Cytometry
• Histocompatibility Antigens Class II (biosynthesis, genetics, immunology)
• Immune Tolerance (immunology)
• Immunomagnetic Separation
• Lymphocyte Activation
• Male
• Mice
• Mice, Inbred C3H
• T-Lymphocytes (immunology, metabolism, pathology)