April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Th1 Cells Express IFN-Gamma, and M1 Macrophages CCL19/CXCL11 and IL-17/IL-18/IL-23 in Sympathetic Ophthalmia
Author Affiliations & Notes
  • C.-C. Chan
    Immunopathology Section, Laboratory of Immunology,
    National Eye Institute/NIH, Bethesda, Maryland
  • D. Shen
    Immunopathology Section, Laboratory of Immunology,
    National Eye Institute/NIH, Bethesda, Maryland
  • R. B. Nussenblatt
    Clinical Immunology Section, Laboratory of Immunology,
    National Eye Institute/NIH, Bethesda, Maryland
  • E. J. Rushing
    Neuropahtology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, Dist. of Columbia
  • E. Furusato
    Immunopathology Section, Laboratory of Immunology,
    National Eye Institute/NIH, Bethesda, Maryland
    Neuropahtology and Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, Dist. of Columbia
  • Footnotes
    Commercial Relationships  C.-C. Chan, None; D. Shen, None; R.B. Nussenblatt, None; E.J. Rushing, None; E. Furusato, None.
  • Footnotes
    Support  NEI Intramural Research Program
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6014. doi:
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      C.-C. Chan, D. Shen, R. B. Nussenblatt, E. J. Rushing, E. Furusato; Th1 Cells Express IFN-Gamma, and M1 Macrophages CCL19/CXCL11 and IL-17/IL-18/IL-23 in Sympathetic Ophthalmia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6014.

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

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Abstract

Purpose: : Sympathetic ophthalmia (SO), a bilateral granulomatous panuveitis following trauma to one eye, is likely an autoimmune inflammatory response toward ocular antigens. The pathology of SO is characterized by diffuse or focal uveal infiltrates of a non-granulomatous inflammation composed of mainly T helper (Th)-lymphocytes, granulomas and Dalen-Fuchs nodules, both composed mainly of macrophages. Recently, Th cells have been subdivided into Th1 (signature cytokines IL-2 and IFN- gamma), Th2 (IL-4, IL-5, and IL-10), and Th17 (IL-17) subsets, while macrophages polarize to M1 (CCL19, CXCL11, and IL-23) and M2 (CCL17 and CCL22) types. This study aims to identify the inflammatory cellular sub-phenotypes in SO.

Methods: : Inflammatory cells that comprise Dalen-Fuchs nodules, granulomas, and non-granulomatous areas were microdissected from archival ocular slides of 5 cases diagnosed with SO, clinically and pathologically. RNA was isolated for RQ-PCR to measure IL-17, IL-18, IL-23, IFN-gamma, CCL19, and CXCL11 transcripts using Taqman gene expression assay. In situ hybridization was used for detection of IL-2, IL-4, and IFN-gamma mRNA expression. Immunohistochemistry with avidin-biotin-complex immunoperoxidase technique was performed to identify positive CD3, CD4, CD8, CD20, CD68, and CD163 cells.

Results: : SO pathology of uveal granulomatous inflammation was illustrated in all 5 cases. The non-granulomatous inflammatory T-cells were mainly CD3 (CD4 > CD8) and expressed IFN-gamma and IL-2, but not IL-4, as reported previously. These cells expressed 10 times higher (10x) IFN-gamma than the cells within the granuloma, indicating that they were Th1 cells. In contrast, the cells from the granulomas and Dalen-Fuchs nodules were mainly CD68+/CD163+/-, and expressed 17x IL-17, 13x IL-18, 8x IL-23, 2x CCL19 and 2x greater CXCL11 than non-granulomatous cells, implying that M1 macrophages represented the predominant cells forming granulomas and Dalen-Fuchs nodules in SO.

Conclusions: : IL-17 appears to be produced by macrophages and not only by Th17 cells. SO is an organ-specific autoimmune disease driven by proinflammatory Th1 and M1 cells. Therefore, targeting Th1 cells, M1 macrophages, and their cytokines/chemokines might provide effective therapeutic agents for SO.

Keywords: uveitis-clinical/animal model • pathology: human • cytokines/chemokines 
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