title: CD4 T cell-dependent conditioning of dendritic cells to produce IL-12 results in CD8-mediated graft rejection and avoidance of tolerance.
abstract: Rejection of ectopic heart transplants expressing OVA requires OVA-specific CD4 and CD8 T cells. In the absence of CD4 T cells, OVA-specific CD8 T cells proliferate and migrate to the graft, but fail to develop cytolytic functions. With CD4 T cells present, clonal expansion of the CD8 T cells is only marginally increased but the cells now develop effector functions and mediate rapid graft rejection. In the presence of CD4 T cells, Ag and B7 levels do not increase on dendritic cells but IL-12 production is up-regulated, and this requires CD154 expression on the CD4 T cells. OVA-specific CD8 T cells lacking the IL-12 receptor fail to differentiate or mediate graft rejection even when CD4 T cells are present. Thus, CD4 T cells condition dendritic cells by inducing the production of IL-12, which is needed as the "third signal" for CD8 T cell differentiation and avoidance of tolerance.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, 55455, USA.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Filatenkov
authors.forename: Erica L
authors.initials: EL
authors.lastname: Jacovetty
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Fischer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Curtsinger
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Mescher
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ingulli
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053707:Receptors, Interleukin-12; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*
chemical_list: D000199:Actins; D019013:CD40 Antigens; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D023201:CD40 Ligand; D018664:Interleukin-12; D010047:Ovalbumin