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

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

Beschreibung

vor 15 Jahren
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�5mmHg 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.

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