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

Chi Hsun Hsieh, Jun Te Hsu, Ya Ching Hsieh, Michael Frink, Raghavan Pillai Raju, William J. Hubbard, Kirby I. Bland, Irshad H. Chaudry

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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-γ were elevated in sham-operated animals, whereas IL-4 and IL-5 rose in the T-H group, revealing a shift from TH1 to TH2 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.

Original languageEnglish (US)
Pages (from-to)1504-1514
Number of pages11
JournalAmerican Journal of Pathology
Volume175
Issue number4
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

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Hemorrhage
T-Lymphocytes
Wounds and Injuries
CTLA-4 Antigen
Ovalbumin
Cytokines
Inbred C3H Mouse
Interleukin-5
Concanavalin A
Interleukin-4
Interleukin-2
Immunization
Up-Regulation
Cell Proliferation
Antigens
In Vitro Techniques

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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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. / Hsieh, Chi Hsun; Hsu, Jun Te; Hsieh, Ya Ching; Frink, Michael; Raju, Raghavan Pillai; Hubbard, William J.; Bland, Kirby I.; Chaudry, Irshad H.

In: American Journal of Pathology, Vol. 175, No. 4, 01.01.2009, p. 1504-1514.

Research output: Contribution to journalArticle

Hsieh, Chi Hsun ; Hsu, Jun Te ; Hsieh, Ya Ching ; Frink, Michael ; Raju, Raghavan Pillai ; Hubbard, William J. ; Bland, Kirby I. ; Chaudry, Irshad H. / 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. In: American Journal of Pathology. 2009 ; Vol. 175, No. 4. pp. 1504-1514.
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