title: Critical role of NKT cells in posttransplant alloantibody production.
abstract: We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.
authors.affiliation: Department of Surgery, Comprehensive Transplant Center, and the College of Medicine, The Ohio State University, Columbus, OH.
authors.forename: J M
authors.initials: JM
authors.lastname: Zimmerer
authors.forename: P
authors.initials: P
authors.lastname: Swamy
authors.forename: P B
authors.initials: PB
authors.lastname: Sanghavi
authors.forename: C L
authors.initials: CL
authors.lastname: Wright
authors.forename: M
authors.initials: M
authors.lastname: Abdel-Rasoul
authors.forename: S M
authors.initials: SM
authors.lastname: Elzein
authors.forename: R R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: G L
authors.initials: GL
authors.lastname: Bumgardner
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007518:Isoantibodies / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D014180:Transplantation
chemical_list: D018106:CD28 Antigens; D007518:Isoantibodies; D015847:Interleukin-4; D007371:Interferon-gamma