The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance.
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.
Lin
Hsi-Hsien
HH
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK.
Faunce
Douglas E
DE
Stacey
Martin
M
Terajewicz
Ania
A
Nakamura
Takahiko
T
Zhang-Hoover
Jie
J
Kerley
Marilyn
M
Mucenski
Michael L
ML
Gordon
Siamon
S
Stein-Streilein
Joan
J
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout
D000943:Antigens, Differentiation; C036763:monocyte-macrophage differentiation antigen