Suppression of activation and costimulatory signaling in splenic CD4+ T cells after trauma-hemorrhage reduces T-cell function: a mechanism of post-traumatic immune suppression.
Reduced immune function is frequently a consequence of serious injury such as trauma-hemorrhage (T-H). Injury may lead to reduced T-cell activation, resulting in decreased engagement of costimulatory molecules after antigen recognition and in subsequent immunological compromise and anergy. We hypothesized that inhibition of CD28 expression is one possible mechanism by which immune functions are suppressed after T-H. Male C3H/HeN mice (with or without ovalbumin immunization) were subjected to sham operation or T-H and sacrificed after 24 hours. Splenic T cells were then stimulated with concanavalin A or ovalbumin in vivo or in vitro, and CD28, cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD69, and phospho-Akt expression was determined. T-cell proliferation/cytokine production was measured in vitro. Stimulation-induced CD69, CD28, and phospho-Akt up-regulation were significantly impaired after T-H compared with sham-operated animals; however, CTLA-4 expression was significantly higher in the T-H group. Over a 3-day span, stimulated T cells from sham-operated animals showed significantly higher proliferation compared with the T-H group. IL-2 and IFN-gamma were elevated in sham-operated animals, whereas IL-4 and IL-5 rose in the T-H group, revealing a shift from T(H)1 to T(H)2 type cytokine production after T-H. Dysregulation of the T-cell costimulatory pathway is therefore likely to be a significant contributor to post-traumatic immune suppression.
Hsieh
Chi-Hsun
CH
Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
Hsu
Jun-Te
JT
Hsieh
Ya-Ching
YC
Frink
Michael
M
Raju
Raghavan
R
Hubbard
William J
WJ
Bland
Kirby I
KI
Chaudry
Irshad H
IH
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation; D006470:Hemorrhage / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D014947:Wounds and Injuries / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; D003208:Concanavalin A; D016207:Cytokines; D037181:Lectins, C-Type; D010047:Ovalbumin; D051057:Proto-Oncogene Proteins c-akt; D000099192:CD69 Antigens; C556707:Ctla4 protein, mouse