title: The role of CD4+CD25+ immunoregulatory T cells in the induction of autoimmune gastritis.
abstract: A number of experimental models of organ-specific autoimmunity involve a period of peripheral lymphopenia prior to disease onset. There is now considerable evidence that the development of autoimmune disease in these models is due to the absence of CD4+CD25+ regulatory T cells. However, the role of CD4+CD25+ regulatory T cells in the prevention of autoimmune disease in normal individuals has not been defined. Here we have assessed the affect of depletion of CD4+CD25+ regulatory T cells in BALB/c mice on the induction of autoimmune gastritis. The CD4+CD25+ T cell population was reduced to 95% of the original population in adult thymectomized mice by treatment with anti-CD25 mAb. By 48 days after the anti-CD25 treatment, the CD4+CD25+ regulatory T cell population had returned to a normal level. Treatment of thymectomized adult mice for up to 4 weeks with anti-CD25 mAb did not result in the development of autoimmune gastritis. Furthermore, we have demonstrated that depletion of CD4+CD25+ regulatory T cells, together with transient CD4+ T lymphopenia, also did not result in the development of autoimmune gastritis, indicating that peripheral expansion of the CD4+ T cell population, per se, does not result in autoimmunity in adult mice. On the other hand, depletion of CD4+CD25+ T cells in 10-day-old euthymic mice resulted in a 30% incidence of autoimmune gastritis. These data suggest that CD4+CD25+ regulatory T cells may be important in protection against autoimmunity while the immune system is being established in young animals, but subsequently other factors are required to initiate autoimmunity.
authors.affiliation: The Russell Grimwade School of Biochemistry and Molecular Biology, The University of Melbourne, Victoria, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Laurie
authors.forename: Ian R
authors.initials: IR
authors.lastname: Van Driel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005756:Gastritis / Q000209:etiology / Q000276:immunology*; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
chemical_list: D015375:Receptors, Interleukin-2