help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2009.081174 on September 3, 2009

Published online before print September 3, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow All Versions of this Article:
ajpath.2009.081174v1
175/4/1504    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Hsieh, C.-H.
Right arrow Articles by Chaudry, I. H.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hsieh, C.-H.
Right arrow Articles by Chaudry, I. H.
(American Journal of Pathology. 2009;175:1504-1514.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081174

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 Raju, William J. Hubbard, Kirby I. Bland and Irshad H. Chaudry

From the Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama

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 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.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society for Investigative Pathology.