Depressed T cell-derived IFN-gamma following trauma-hemorrhage: a potential mechanism for diminished APC responses.
BACKGROUND
Prolonged immunosuppression has been demonstrated after trauma-hemorrhage resulting in an increased susceptibility to sepsis. The contribution of antigen-presenting cells (APC) vs T cells to this diminished immune response, however, remains unknown.


METHODS
To study this, male mice were trauma-hemorrhaged (35 +/- 5 mmHg for 90 min and resuscitation) or sham operated. At 24 h thereafter, spleens were harvested and T cells (via Microbeads) and APC (via adherence) were isolated. Cocultures of combined T cells and APC were established for 48 h, stimulated with ConA and LPS. The T cell-derived cytokine IFN-gamma and IL-12 for APC responses were measured in the supernatants by the multiplex assay.


RESULTS
The release of IFN-gamma was suppressed by T cells after trauma-hemorrhage irrespective of whether sham or trauma-hemorrhage APC were added. Trauma-hemorrhaged APC did not affect T cells-derived IFN-gamma release by sham T cells. In contrast, trauma-hemorrhaged T cells depressed the release of IL-12 by APC. The release of IL-12 by trauma-hemorrhaged APC was not altered when sham T cells were cocultured.


CONCLUSIONS
Prolonged immunosuppression after trauma-hemorrhage appears to be predominantly due to diminished T cell function. Thus, attempts to prevent immunodysfunction should be directed towards T cells.
Walz
C R
CR
Department of Surgery, Klinikum Grosshadern, Ludwig Maximillian University, Marchioninistrasse 15, 81377 Munich, Germany.
Zedler
S
S
Schneider
C P
CP
Mayr
S
S
Loehe
F
F
Bruns
C J
CJ
Faist
E
E
Jauch
K W
KW
Angele
M K
MK
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000032:analysis*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011897:Random Allocation; D017471:Receptors, Interferon / Q000032:analysis*; D012771:Shock, Hemorrhagic / Q000276:immunology* / Q000628:therapy; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014947:Wounds and Injuries / Q000276:immunology; D000096743:Interferon gamma Receptor
D018664:Interleukin-12; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor