Depressed T cell-derived IFN-γ following trauma-hemorrhage: a potential mechanism for diminished APC responses

Walz, C. R.; Zedler, Siegfried; Schneider, Christian; Mayr, Stefan; Loehe, Florian; Bruns, Christiane; Faist, Eugen; Jauch, Karl Walter; Angele, Martin K.

doi:10.1007/s00423-007-0164-7

Cited by 19 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[10][11][12] Defective immune responses have been shown for both T-cells and APCs following trauma and severe blood loss. In this regard, T-cells exhibit reduced capacities to proliferate and to release cytokines such as IL-2 and IFN-g. 2,13 Similar to T-cells, APCs function is also suppressed following trauma-hemorrhage, as indicated by decreased cytokine releases and reduced antigen presentation via diminished MHC II expression. 2,4 In those studies, however, T-cells and APCs were not separated prior …”

Section: Discussionmentioning

confidence: 99%

“…15 Similarly, recent studies by our group using a co-culture system following immune cell separation demonstrated that trauma-hemorrhaged T-cells are able to depress IL-12 release by APCs. 2 However, the release of the T-cell cytokine IFN-g remained unaffected by trauma-hemorrhaged APCs. These results suggested that dysfunctional T-cells might be primarily responsible for the persistent immunosuppression observed following trauma-hemorrhage.…”

Section: T -H a P C T -H T C T -H A P C T -H T C S H A Mmentioning

confidence: 99%

“…2,20,21 This stimulation protocol results in an activation of T-cells and APCs in vitro. 22,23 Recently, LPS-activated monocytes have been demonstrated to suppress T-cell immune responses.…”

Section: T -H a P C T -H T C T -H A P C T -H T C S H A Mmentioning

confidence: 99%

“…2 The capacity of APCs and T-cells to release cytokines upon in vitro stimulation has been shown to reflect immune cell function. The present work further extends those results by measuring concentrations of an additional Th1 cytokine, IL-2, and the Th2 cytokines IL-4 and IL-10.…”

Section: T -H a P C T -H T C T -H A P C T -H T C S H A Mmentioning

confidence: 99%

“…T-cells) immunity is thought to play a pivotal role in the induction of an adequate cell-mediated immune response. 2,3 Alterations in the immune response of APCs and T-cells have been demonstrated following trauma and blood loss. In particular, MHC class II expression is suppressed on APCs resulting in decreased antigen presentation capacities following trauma-hemorrhage.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

et al. 2009

View full text Add to dashboard Cite

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 AE 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 traumahemorrhage animals depressed MHC class II expression of CD11c(þ) 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.

show abstract