Intercellular adhesion molecule 1 mediates migration of Th1 and Th17 cells across human retinal vascular endothelium.

Arpita Bharadwaj, Lauren Schewitz-Bowers, Lai Wei, Richard Lee, Justine Smith

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    PURPOSE. Autoimmune inflammation of the retina causes vision loss in the majority of affected individuals. Th1 or Th17 cells initiate the disease on trafficking from the circulation into the eye across the retinal vascular endothelium. We investigated the ability of human Th1- and Th17-polarized cells to cross a simulated human retinal endothelium, and examined the role of IgG superfamily members in this process.

    METHODS. Th1- and Th17-polarized cell populations were generated from human peripheral blood CD4+ T cells, using two Th1- and Th17-polarizing protocols. Transendothelial migration assays were performed over 18 hours in Boyden chambers, after seeding the transwell membrane with human retinal endothelial cells. In some assays intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), or activated leukocyte cell adhesion molecule (ALCAM) blocking antibody, or isotype- and concentrationmatched control antibody, was added to the upper chambers.

    RESULTS. Th1- and Th17-polarized cells migrated equally efficiently across the human retinal endothelial monolayer. The percentage of IL-17+ IFN-γ Th17-polarized cells was reduced following migration. Blocking ICAM-1, but not VCAM-1 or ALCAM, significantly reduced migration of Th1- and Th17-polarized cells for a majority of human donors.

    CONCLUSIONS. Taken in the context of other literature on transendothelial migration, our results illustrate the importance of investigating the specific tissue and vascular endothelium when considering helper T cell migration in autoimmune inflammation. Our findings further indicate that while generalizations about involvement of specific adhesion molecules in uveitis and other autoimmune disease may be possible, these may not apply to individual patients universally. The observations are relevant to the use of adhesion blockade for therapeutic purposes.

    Original languageEnglish
    Pages (from-to)6917-6925
    Number of pages9
    JournalInvestigative Ophthalmology and Visual Science
    Volume54
    Issue number10
    DOIs
    Publication statusPublished - 2014

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