Mechanism of immunosuppression following hemorrhage: defective antigen presentation by macrophages.
The mechanism by which simple hemorrhage profoundly impairs the proliferative response of T lymphocytes to mitogen and alloantigen, produces a defect in interleukin-2 generation, and increases the susceptibility to sepsis remains unknown. Since antigen presentation (AP) by the macrophage (M phi) plays a critical role in the antigen-specific activation of T-helper cells and lymphokine production, we investigated whether the function of the M phi as an AP cell is altered following hemorrhage. C3H/HEJ mice were bled to a mean BP of 35 mm Hg, maintained at that level for 1 hr, and then resuscitated. There was no mortality with this model. Control mice were not bled but otherwise treated identically. Immediately after resuscitation the mice were sacrificed and peritoneal M phi (PM phi) as well as splenic adherent cells (SAC) were harvested. AP function was tested by coculturing different numbers of PM phi and SAC with D10.G4.1 cells (2 x 10(4) cells/well) in the presence of conalbumin (300 micrograms/ml). This T-helper cell clone proliferates upon recognition of conalbumin in the context of Iak (a M phi surface membrane glycoprotein), thus directly reflecting M phi AP capability. After 72 hr of incubation, the cultures were pulsed with [3H]thymidine and harvested. D10.G4.1 proliferations induced via AP by PM phi and SAC from hemorrhaged-resuscitated mice were 29 and 24% of control, respectively (P less than 0.05). Thus, we conclude that AP by M phi following hemorrhage is defective despite adequate resuscitation, a mechanism which could explain the state of immunosuppression and enhanced susceptibility to sepsis.
Stephan
R N
RN
Department of Surgery, Michigan State University, East Lansing 48824.
Ayala
A
A
Harkema
J M
JM
Dean
R E
RE
Border
J R
JR
Chaudry
I H
IH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001696:Biomechanical Phenomena; D006470:Hemorrhage / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology