Regulatory T Cells Occupy an Isolated Niche in the Intestine that Is Antigen Independent

• There is a unique niche for regulatory T cells in the intestinal lamina propria (LP)
• This niche can be filled and maintained independently of MHC class II and IL-2
• Parabiosis shows that the niche is closed as lamina propria Tregs do not circulate
• Maintenance of MHCII-independent LP Tregs does depend upon commensal bacteria

SummaryRegulatory 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.

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