title: Regulatory T cells occupy an isolated niche in the intestine that is antigen independent.
abstract: Regulatory T cells (Tregs) are CD4(+) T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4(+) T cells, Tregs require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requirement for MHCII in Treg homeostasis in tissues such as intestinal lamina propria (LP) is unknown. We examined LP Treg homeostasis in a transgenic mouse model that lacks peripheral TCR-MHCII interactions and generation of extrathymic Tregs (iTregs). Thymically generated Tregs entered the LP of weanlings and proliferated independently of MHCII to fill the compartment. The adult LP was a closed niche; new thymic Tregs were excluded, and Tregs in parabiotic pairs were LP resident. The isolated LP niche was interleukin-2 (IL-2) independent but dependent on commensal bacteria. Thus, an LP Treg niche can be filled, isolated, and maintained independently of antigen signals and iTregs. This niche may represent a tissue-specific mechanism for maintaining immune tolerance.
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Korn
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Harper G
authors.initials: HG
authors.lastname: Hubbeling
authors.affiliation: Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Paige M
authors.initials: PM
authors.lastname: Porrett
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Barnett
authors.affiliation: Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. Electronic address: tlaufer@mail.med.upenn.edu.
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
mesh_terms: D000818:Animals; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D007108:Immune Tolerance; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II