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

Xunbao Duan, David Yarmush, Avrum Leeder, Martin L. Yarmush, Richard N. Mitchell

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16 Scopus citations


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-γ (IFN-γ-/-). The results are consistent with immunosuppression attributable to burninduced IFN-γ production, which in turn, drives macrophage NO synthesis (NOS). In MLR cultures, lymphocyte proliferation and IFN-γ 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-γ-/- splenocytes did not restore the MLR response of burned splenocytes. T cells from burned IFN-γ-/- 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-γ or NO production.

Original languageEnglish (US)
Pages (from-to)305-313
Number of pages9
JournalJournal of Leukocyte Biology
Issue number2
StatePublished - Feb 2 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology


  • Antigen-presenting cells
  • Costimulation
  • Immune suppression
  • T lymphocytes


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