title: In vivo administration of interleukin-2 turns on anergic self-reactive T cells and leads to autoimmune disease.
abstract: One major mechanism of self tolerance involves the deletion of T cell clones in the thymus. In athymic mice, tolerance to self antigens must be generated extrathymically. T cells with self-reactive receptors undergo either peripheral clonal deletion or become unresponsive (i.e. anergic). The unresponsive state of human and mouse T cell clones in vitro can be reversed by the addition of exogenous interleukin (IL)-2, thus transforming anergic T cells to an activated state. Here it is shown that the in vivo delivery of IL-2 to athymic BALB/c nu/nu mice abrogates the anergic state of self-reactive V beta 3+ and V beta 11+ T cells [which are normally deleted in the minor lymphocyte stimulatory (Mls)-1b-, I-E(+)-expressing euthymic counterparts]. Thus, V beta 3+ and V beta 11+ T cells from IL-2-treated nude mice proliferate in response to T cell receptor cross-linking and acquire effector functions as measured by their ability to deliver aid to B cells upon specific stimulation. This activation correlates with the development of autoimmune manifestations (DNA autoantibodies, rheumatoid factors, erythroleukopenia and minimal change nephritis) in these IL-2-treated mice.
authors.affiliation: Basel Institute for Immunology, Universidad Autónoma de Madrid.
authors.forename: J C
authors.initials: JC
authors.lastname: Gutierrez-Ramos
authors.forename: I
authors.initials: I
authors.lastname: Moreno de Alboran
authors.forename: C
authors.initials: C
authors.lastname: Martínez
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta