Recruitment of IFN-γ-Producing (Th1-Like), Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Sellectin Glycoprotein Ligand 1:P/E-Selectin Interactions

Heping Xu*, Ayyakkannu Manivannan, Hui Rong Jiang, Janet Liversidge, Peter F. Sharp, John V. Forrester, Isabel J. Crane

*Corresponding author for this work

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Although there is evidence that altering the Th1/Th2 balance toward Th2 cells may be important in the resolution of Th1-type autoimmune disease, adoptive transfer of Th2 cells is not effective in protecting against Th1-type disease and may cause disease. Therefore, we examined the recruitment of Th1- and Th2-like cells into the retina in the murine autoimmune disease experimental autoimmune uveoretinitis. CD4 T cells were polarized in vitro to IFN-γ-producing Th1-like cells and non-IFN-γ-producing Th2-like cells, labeled, and adoptively transferred. Trafficking to the retina in vivo was evaluated by scanning laser opthalmoscopy and infiltration by confocal microscopy. There were more rolling and adherent Th1-like cells and they rolled more slowly than did Th2-like cells. Th1-like cells were preferentially recruited into the retinal parenchyma at both initiation and resolution. Surface P-selectin glycoprotein ligand 1 (PSGL-1) and LFA-1 were up-regulated on both populations but were expressed at higher levels on Th1-like cells. Up-regulation of CD44 expression was higher on Th2-like cells. P-selectin, E-selectin, and ICAM-1 are up-regulated on postcapillary venules in the retina. Pretreatment of Th1-like cells with anti-PSGL-1 inhibited rolling and infiltration of Th1-like cells but not Th2-like cells, providing direct in vivo evidence for the inability of Th2 to respond to P/E-selectin despite increased expression of PSGL-1. Anti-LFA-1 pretreatment inhibited infiltration of both Th1- and Th2-like cells, but more so Th-1. We suggest that random trafficking of activated T cells (both Th1 and Th2) across the blood-retina barrier is mediated by CD44:CD44R and LFA-1:1CAM-1, whereas preferential recruitment of Th1 cells is mediated by PSGL-1:P/E-selectin.

Original languageEnglish
Pages (from-to)3215-3224
Number of pages10
JournalJournal of Immunology
Volume172
Issue number5
Publication statusPublished - 1 Mar 2004

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ASJC Scopus subject areas

  • Immunology

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