HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print November 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0407228v1 83/2/305    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Duan, X. Articles by Mitchell, R. N. Search for Related Content PubMed PubMed Citation Articles by Duan, X. Articles by Mitchell, R. N.

(Journal of Leukocyte Biology. 2008;83:305-313.)
© 2008 by Society for Leukocyte Biology

Burn-induced immunosuppression: attenuated T cell signaling independent of IFN-- and nitric oxide-mediated pathways

Xunbao Duan^*,1,2, David Yarmush^*,1, Avrum Leeder^*, Martin L. Yarmush^* and Richard N. Mitchell^,3

^* The Surgical Services/Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children, Boston, Massachusetts, USA; and
Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA

³ Correspondence: Department of Pathology, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur/NRB 730D, Boston, MA 02115, USA. E-mail: rmitchell{at}rics.bwh.harvard.edu

ABSTRACT

Burn injury results in immunosuppression; previous work implicated a combination of altered T lymphocyte subpopulations and the elaboration of macrophage-derived mediators. However, the conclusions were based on T cell stimulations in the setting of high-dose polyclonal mitogenic stimuli and a single kinetic time-point. In this study, splenocytes from burned animals were used to examine lymphocyte responses over a multi-day time course following saturating and subsaturating anti-CD3, as well as mixed lymphocyte response (MLR) stimulation. Burn injury resulted in suppressed splenocyte-proliferative responses to high-dose anti-CD3 (2 µg/ml) at all culture time-points (Days 2–5); this inhibition was eliminated by removing macrophages from the splenocyte cultures, by blocking NO production, or by using splenocytes from burned animals congenitally deficient in IFN- (IFN-^–/–). The results are consistent with immunosuppression attributable to burn-induced IFN- production, which in turn, drives macrophage NO synthesis (NOS). In MLR cultures, lymphocyte proliferation and IFN- production were depressed at later time-points (Days 3–5). APC from burned animals showed no defects as MLR stimulators; T cells from burned animals showed defective, proliferative responses, regardless of the stimulator population. Removing macrophages, adding a NOS inhibitor, or using IFN-^–/– splenocytes did not restore the MLR response of burned splenocytes. T cells from burned IFN-^–/– animals also showed depressed proliferation with subsaturating levels of anti-CD3 (0.1 µg/ml); anti-CD-28 augmented the proliferative response. We conclude that burn-induced immunosuppression to authentic antigenic stimulation is related at least in part to defective CD3 signaling pathways and not simply to increased IFN- or NO production.

Key Words: immune suppression • T lymphocytes • antigen-presenting cells • costimulation