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

Lin, Hsi-Hsien; Faunce, Douglas E.; Stacey, Martin; Terajewicz, Ania; Nakamura, Takahiko; Zhang-Hoover, Jie; Kerley, Marilyn; Mucenski, Michael L.; Gordon, Siamon; Stein-Streilein, Joan

doi:10.1084/jem.20042307

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

Journal Article · Mon May 09 00:00:00 EDT 2005 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.20042307· OSTI ID:1625187

Lin, Hsi-Hsien ^[1]; Faunce, Douglas E. ^[2]; Stacey, Martin ^[3]; Terajewicz, Ania ^[4]; Nakamura, Takahiko ^[4]; Zhang-Hoover, Jie ^[5]; Kerley, Marilyn ^[6]; Mucenski, Michael L. ^[7]; Gordon, Siamon ^[3]; Stein-Streilein, Joan ^[8]

Univ. of Oxford (United Kingdom). Sir William Dunn School of Pathology; Chang Gung Univ., Tao-Yuan (Taiwan). Dept. of Microbiology and Immunology; DOE/OSTI
Harvard Medical School, Boston, MA (United States). Schepens Eye Research Inst.; National Eye Institute Training Program in the Molecular Bases of Eye Diseases, Bethesda, MD (United States)
Univ. of Oxford (United Kingdom). Sir William Dunn School of Pathology
Harvard Medical School, Boston, MA (United States). Schepens Eye Research Inst.
Harvard Medical School, Boston, MA (United States). Schepens Eye Research Inst.; Harvard Medical School, Boston, MA (United States). Brigham and Women's Hospital. Dept. of Medicine. Pulmonary and Critical Care Division
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Life Sciences Division
Cincinnati Children's Hospital Medical Center, Cincinnati, OH (United States). Division of Pulmonary Biology
Harvard Medical School, Boston, MA (United States). Schepens Eye Research Inst.; Harvard Medical School, Boston, MA (United States). Brigham and Women's Hospital. Dept. of Medicine. Pulmonary and Critical Care Division

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

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1625187

Journal Information:: Journal of Experimental Medicine, Journal Name: Journal of Experimental Medicine Journal Issue: 10 Vol. 201; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Anti-Colitic Effects of Ethanol Extract of Persea americana Mill. through Suppression of Pro-Inflammatory Mediators via NF-κB/STAT3 Inactivation in Dextran Sulfate Sodium-Induced Colitis Mice Hong, Joo Young; Chung, Kyung-Sook; Shin, Ji-Sun International Journal of Molecular Sciences, Vol. 20, Issue 1 https://doi.org/10.3390/ijms20010177	journal	January 2019
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Tolerance Induced by Apoptotic Antigen-Coupled Leukocytes Is Induced by PD-L1 ⁺ and IL-10–Producing Splenic Macrophages and Maintained by T Regulatory Cells Getts, Daniel R.; Turley, Danielle M.; Smith, Cassandra E. The Journal of Immunology, Vol. 187, Issue 5 https://doi.org/10.4049/jimmunol.1004175	journal	August 2011
F4/80 ⁺ Alternatively Activated Macrophages Control CD4 ⁺ T Cell Hyporesponsiveness at Sites Peripheral to Filarial Infection Taylor, Matthew D.; Harris, Anjanette; Nair, Meera G. The Journal of Immunology, Vol. 176, Issue 11 https://doi.org/10.4049/jimmunol.176.11.6918	journal	May 2006
γδ T Cells Promote Anterior Chamber-Associated Immune Deviation and Immune Privilege through Their Production of IL-10 Ashour, Hossam M.; Niederkorn, Jerry Y. The Journal of Immunology, Vol. 177, Issue 12 https://doi.org/10.4049/jimmunol.177.12.8331	journal	December 2006
Sialoadhesin Promotes the Inflammatory Response in Experimental Autoimmune Uveoretinitis Jiang, Hui-Rong; Hwenda, Lenias; Makinen, Kimmo The Journal of Immunology, Vol. 177, Issue 4 https://doi.org/10.4049/jimmunol.177.4.2258	journal	August 2006
Recruitment and Activation of Macrophages by Pathogenic CD4 T Cells in Type 1 Diabetes: Evidence for Involvement of CCR8 and CCL1 Cantor, Joseph; Haskins, Kathryn The Journal of Immunology, Vol. 179, Issue 9 https://doi.org/10.4049/jimmunol.179.9.5760	journal	October 2007
Macrophages as APC and the Dendritic Cell Myth Hume, David A. The Journal of Immunology, Vol. 181, Issue 9 https://doi.org/10.4049/jimmunol.181.9.5829	journal	October 2008
Ocular Immune Privilege Hori, Junko Journal of The Society of Japanese Women Scientists, Vol. 8, Issue 1 https://doi.org/10.5939/sjws.07002	journal	January 2007

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