TY - JOUR
T1 - Murine dendritic cell antigen-presenting cell function is not altered by burn injury
AU - Fujimi, Satoshi
AU - Lapchak, Peter H.
AU - Zang, Yan
AU - MacConmara, Malcolm P.
AU - Maung, Adrian A.
AU - Delisle, Adam J.
AU - Mannick, John A.
AU - Lederer, James A.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Severe injury disrupts normal immune regulation causing a transient hyperinflammatory reaction and suppressed adaptive immune function. This report addresses the potential contribution of dendritic cells (DC) to changes in adaptive immune function after injury by specifically measuring injury-induced changes in splenic DC numbers and subsets, cell-surface markers, TLR responses, and APC function. Using a mouse burn injury model, we found that injury did not markedly alter the relative percentage of lymphoid, myeloid, or plasmacytoid DC in the spleens of burninjured mice. Moreover, we did not observe a significant reduction in cell-surface expression of several major costimulatory molecules, CD40, CD80, CD86, programmed death 1 ligand, ICOS ligand, and B7-H3, on DC. Instead, we observed increased cell-surface expression of CD86 at 1 day after injury with no significant changes in costimulatory molecule expression at 7 days after injury, suggesting that burn injury causes an early activation of DC. In addition, injury did not suppress DC reactivity to TLR2, TLR4, or TLR9 agonists. Most important, DC prepared from injured mice were able to present peptide antigen to naïve OTII TCR transgenic CD4+ T cells as efficiently and effectively as DC from sham-injured mice. We also found that CD4 T cells stimulated with antigen presented by DC from sham or burn mice showed similar levels of IL-2, IFN-γ, IL-10, and IL-13 production. Taken together, these findings support the conclusion that DC do not acquire a suppressive phenotype following severe injury in mice.
AB - Severe injury disrupts normal immune regulation causing a transient hyperinflammatory reaction and suppressed adaptive immune function. This report addresses the potential contribution of dendritic cells (DC) to changes in adaptive immune function after injury by specifically measuring injury-induced changes in splenic DC numbers and subsets, cell-surface markers, TLR responses, and APC function. Using a mouse burn injury model, we found that injury did not markedly alter the relative percentage of lymphoid, myeloid, or plasmacytoid DC in the spleens of burninjured mice. Moreover, we did not observe a significant reduction in cell-surface expression of several major costimulatory molecules, CD40, CD80, CD86, programmed death 1 ligand, ICOS ligand, and B7-H3, on DC. Instead, we observed increased cell-surface expression of CD86 at 1 day after injury with no significant changes in costimulatory molecule expression at 7 days after injury, suggesting that burn injury causes an early activation of DC. In addition, injury did not suppress DC reactivity to TLR2, TLR4, or TLR9 agonists. Most important, DC prepared from injured mice were able to present peptide antigen to naïve OTII TCR transgenic CD4+ T cells as efficiently and effectively as DC from sham-injured mice. We also found that CD4 T cells stimulated with antigen presented by DC from sham or burn mice showed similar levels of IL-2, IFN-γ, IL-10, and IL-13 production. Taken together, these findings support the conclusion that DC do not acquire a suppressive phenotype following severe injury in mice.
KW - CD4 T cells
KW - Costimulatory molecules
KW - Th1
KW - Th2
KW - Toll-like receptors
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U2 - 10.1189/jlb.0408257
DO - 10.1189/jlb.0408257
M3 - Article
C2 - 19228816
AN - SCOPUS:65549124973
SN - 0741-5400
VL - 85
SP - 862
EP - 870
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -