title: Burn injury initiates a shift in superantigen-induced T cell responses and host survival.
abstract: Severe injury induces a temporal shift in immune reactivity that can cause serious complications or even death. We previously reported that mice exposed to bacterial superantigen (SAg) early after injury undergo a strong SAg response with lethal consequences. This study compares the early and late effects of burn injury on SAg reactivity in vivo to establish how injury influences adaptive immune responses. We found that mice challenged with ordinarily sublethal doses of staphylococcal enterotoxin A or staphylococcal enterotoxin B at 1 day after burn injury exhibited high mortality, whereas no mortality occurred at 7 days after injury. This shift in mortality correlated with higher Th2-type cytokines (IL-4 and IL-10) being expressed by CD4(+) and CD8(+) T cells from burn as opposed to sham mice at 7 days after injury. Lymph node cells from burn-injured mice also produced higher levels of Th2-type cytokines at 7 days after injury. The results of cell-mixing studies using CD4(+) and CD8(+) T cells mixed with APCs from sham or burn mice suggested that changes in both T cells and APCs are involved in the altered SAg response. Finally, the biological significance of altered SAg reactivity following injury was shown by demonstrating that blocking IL-10 activity in vivo caused higher SAg-induced mortality at 7 days after injury. These findings support the idea that injury promotes a Th2-type shift in adaptive immune reactivity. Although prior studies link this counterinflammatory-type response to lowered resistance to infection, the present results suggest it may sometimes benefit the injured host.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zang
authors.forename: Sinead M
authors.initials: SM
authors.lastname: Dolan
authors.forename: Niamh
authors.initials: N
authors.lastname: Ni Choileain
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Kriynovich
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Murphy
authors.forename: Peter
authors.initials: P
authors.lastname: Sayles
authors.forename: John A
authors.initials: JA
authors.lastname: Mannick
authors.forename: James A
authors.initials: JA
authors.lastname: Lederer
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002056:Burns / Q000150:complications / Q000276:immunology* / Q000401:mortality*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012774:Shock, Traumatic / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000008:administration & dosage* / Q000276:immunology; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; D016753:Interleukin-10; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal