The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance.

Journal article

We show that the mouse macrophage-restricted F4/80 protein is not required for the development and distribution of tissue macrophages but is involved in the generation of antigen-specific efferent regulatory T (T reg) cells that suppress antigen-specific immunity. In the in vivo anterior chamber (a.c.)-associated immune deviation (ACAID) model of peripheral tolerance, a.c. inoculation of antigen into F4/80(-/-) mice was unable to induce efferent T reg cells and suppress delayed-type hypersensitivity (DTH) responses. Moreover, the use of anti-F4/80 mAb and F4/80(-/-) APCs in an in vitro ACAID model showed that all APC cells in the culture must be able to express F4/80 protein if efferent T reg cells were to be generated. In a low-dose oral tolerance model, WT but not F4/80(-/-) mice generated an efferent CD8(+) T reg cell population that suppressed an antigen-specific DTH response. Peripheral tolerance was restored in F4/80(-/-) mice by adoptive transfer of F4/80(+) APCs in both peripheral tolerance models, indicating a central role for the F4/80 molecule in the generation of efferent CD8(+) T reg cells.

Authors: Lin, H; Faunce, D; Stacey, M; Terajewicz, A; Nakamura, T

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 201
• Issue: 10
• Pages: 1615-1625
• Publication date: 2005-05-01
• DOI: 10.1084/jem.20042307
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Animals; CD8-Positive T-Lymphocytes; Immune Tolerance; Mice; Cell Movement; Mice, Knockout; Hypersensitivity, Delayed; Dendritic Cells; Antigen Presentation; Antigens, Differentiation; Cell Differentiation; Adoptive Transfer; Macrophages