title: CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.
abstract: Self-antigens expressed in extrathymic tissues such as the pancreas can be transported to draining lymph nodes and presented in a class I-restricted manner by bone marrow-derived antigen-presenting cells. Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion. In this report, we investigate the influence of CD4+ T cell help on this process. Small numbers of autoreactive OVA-specific CD8+ T cells were unable to cause diabetes when adoptively transferred into mice expressing ovalbumin in the pancreatic beta cells. Coinjection of OVA-specific CD4+ helper T cells, however, led to diabetes in a large proportion of mice (68%), suggesting that provision of help favored induction of autoimmunity. Analysis of the fate of CD8+ T cells indicated that CD4(+) T cell help impaired their deletion. These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Kurts
authors.forename: F R
authors.initials: FR
authors.lastname: Carbone
authors.forename: M
authors.initials: M
authors.lastname: Barnden
authors.forename: E
authors.initials: E
authors.lastname: Blanas
authors.forename: J
authors.initials: J
authors.lastname: Allison
authors.forename: W R
authors.initials: WR
authors.lastname: Heath
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology
chemical_list: D001324:Autoantigens; D010047:Ovalbumin