title: CD4+CD25+ T cell-dependent inhibition of autoimmunity in transgenic mice overexpressing human Bcl-2 in T lymphocytes.
abstract: Regulation of lymphocyte survival is essential for the maintenance of lymphoid homeostasis preventing the development of autoimmune diseases. Recently, we described a systemic lupus erythematosus associated with an IgA nephropathy in autoimmune-prone (NZW x C57BL/6)F(1) overexpressing human Bcl-2 (hBcl-2) in B cells (transgenic (Tg) 1). In the present study, we analyze in detail a second line of hBcl-2 Tg mice overexpressing the transgene in all B cells and in a fraction of CD4(+) and CD8(+) T cells (Tg2). We demonstrate here that the overexpression of hBcl-2 in T cells observed in Tg2 mice is associated with a resistance to the development of lupus disease and collagen type II-induced arthritis in both (NZW x C57BL/6)F(1) and (DBA/1 x C57BL/6)F(1) Tg2 mice, respectively. The disease-protective effect observed in autoimmune-prone Tg2 mice is accompanied by an increase of peripheral CD4(+)CD25(+) hBcl-2(+) regulatory T cells (T(regs)), expressing glucocorticoid-induced TNFR, CTLA-4, and FoxP3. Furthermore, the in vivo depletion of CD4(+)CD25(+) T(regs) in (DBA/1 x C57BL/6)F(1) Tg2 mice promotes the development of a severe collagen type II-induced arthritis. Taken together, our results indicate that the overexpression of hBcl-2 in CD4(+) T cells alters the homeostatic mechanisms controlling the number of CD4(+)CD25(+) T(regs) resulting in the inhibition of autoimmune diseases.
authors.affiliation: Departamento de Biología Molecular (Unidad asociada al Centro de Investigaciones Biológicas/Consejo Superior de Investigaciones Científicas), Universidad de Cantabria, Cardenal Herrera Oria s/n, 39011 Santander, Spain.
authors.forename: Jovanna
authors.initials: J
authors.lastname: González
authors.forename: Esther
authors.initials: E
authors.lastname: Tamayo
authors.forename: Inés
authors.initials: I
authors.lastname: Santiuste
authors.forename: Regina
authors.initials: R
authors.lastname: Marquina
authors.forename: Luis
authors.initials: L
authors.lastname: Buelta
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Shozo
authors.initials: S
authors.lastname: Izui
authors.forename: Marcos
authors.initials: M
authors.lastname: López-Hoyos
authors.forename: Jesús
authors.initials: J
authors.lastname: Merino
authors.forename: Ramón
authors.initials: R
authors.lastname: Merino
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000633:toxicity; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D024043:Collagen Type II; D019253:Proto-Oncogene Proteins c-bcl-2