title: Injury-induced suppression of effector T cell immunity requires CD1d-positive APCs and CD1d-restricted NKT cells.
abstract: Overwhelming infection remains the leading cause of death from serious burn injury despite recent advances in the care of burn patients and a better understanding of immune and inflammatory consequences of injury. In this study, we report a critical requirement for CD1d-restricted NKT cells and CD1d expression by APCs in the immune dysfunction that occurs early after burn injury. Using a well-established murine scald injury model with BALB/c and BALB/c CD1d knockout mice, we investigated whether peripheral T cell immunity was affected by the presence or absence of CD1d-restricted NKT cells in the early stages after injury. Using Ag-specific delayed-type hypersensitivity, T cell proliferation, and cytokine production as indices of immune responsiveness, we observed that both CD1d expression by APCs and CD1d-restricted NKT cells are required for immune suppression after injury. Via adoptive transfer of splenocytes from injured mice to uninjured recipients, we found injury-induced suppression of immunity to be Ag specific, long lasting, and critically dependent on cell surface expression of CD1d by APCs. Together, our results suggest that the defects in T cell responsiveness that occur subsequent to severe burn injury are not merely the result of global or passive suppression, but instead represent an active form of CD1d/NKT cell-dependent immunologic tolerance.
authors.affiliation: Department of Surgery, and Burn and Shock Trauma Institute, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Palmer
authors.forename: Julia M
authors.initials: JM
authors.lastname: Tulley
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Faunce
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018949:Antigens, CD1 / Q000096:biosynthesis* / Q000235:genetics; D055610:Antigens, CD1d; D002056:Burns / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance / Q000235:genetics; D007111:Immunity, Cellular / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D015847:Interleukin-4; D007371:Interferon-gamma