May 2005
Volume 46, Issue 13
ARVO Annual Meeting Abstract  |   May 2005
Selective Unresponsiveness of TNFRp55–/– Macrophages to IFN Stimulation
Author Affiliations & Notes
  • C.J. Calder
    Bristol University, Bristol, United Kingdom
  • L.B. Nicholson
    Pathology & Microbiology,
    Bristol University, Bristol, United Kingdom
  • A.D. Dick
    Bristol University, Bristol, United Kingdom
  • Footnotes
    Commercial Relationships  C.J. Calder, None; L.B. Nicholson, None; A.D. Dick, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1043. doi:
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      C.J. Calder, L.B. Nicholson, A.D. Dick; Selective Unresponsiveness of TNFRp55–/– Macrophages to IFN Stimulation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1043.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract: : Purpose:Activated macrophages are largely responsible for effecting tissue destruction in the retina during Experimental Autoimmune Uveoretinitis (EAU). To dissect the role of TNF signalling in macrophages, we studied EAU in mice deficient in TNFRp55 (TNFR1). Methods: EAU was induced in TNFRp55–/– and WT mice following immunisation with Interphotoreceptor retinoid binding protein (IRBP) residues 1–20. At different time point eyes were enucleated and spleens dissected for histological disease score and functional assessment, respectively. Bone–marrow derived–macrophages (BM–MΦ) were generated in TeflonTM bags containing M–CSF media and stimulated in vitro with TNFα and IFNγ. Results: TNFRp55–/– mice developed less severe EAU than controls, with concomitant reduction in antigen–specific splenocyte proliferation and production of IFNγ and IL–2. In vitro studies using (BM–MΦ) from TNFRp55–/– and WT mice, showed that following stimulation with IFNγ, TNFRp55–/– BM–MΦ did not produce nitrite or up–regulate CD40 expression. However, we found no difference in expression of MHC class II or IFNγR (CD119) between TNFRp55–/– and WT. Blockade with sTNFr–Ig fusion protein, during stimulation with IFNγ, converted WT BM–MΦ to the same phenotype as TNFRp55–/– mice. Conclusions: Nitrite production, but not MHCII upregulation, relies on autocrine stimulation of macrophages by TNFα mediated through the TNFRp55 but not TNFRp75. In the absence of this signal, IFNγ is not sufficient to induce complete macrophage activation.

Keywords: autoimmune disease • nitric oxide 

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