Recruitment of IFN-¿-producing (Th1-like) cells into the inflamed retina in vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin interactions

Heping Xu, Ayyakkannu Manivannan, Hui-Rong Jiang, Janet Mary Liversidge, Peter Frederick Sharp, John Vincent Forrester, Isabel Joan Crane

Research output: Contribution to journalArticlepeer-review

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-gamma-producing Th1-like cells and non-IFN-gamma-producing Th2-like cells, labeled, and adoptively transferred. Trafficking to the retina in vivo was evaluated by scanning laser ophthalmoscopy 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:ICAM-1, whereas preferential recruitment of Th1 cells is mediated by PSGL-1:P/E-selectin.

Original languageEnglish
Pages (from-to)3215-3224
Number of pages9
JournalThe Journal of Immunology
Volume172
Issue number5
Publication statusPublished - Mar 2004

Keywords

  • EXPERIMENTAL AUTOIMMUNE UVEORETINITIS
  • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
  • DIABETIC NOD MICE
  • TH2 CELLS
  • T-CELLS
  • TRANSENDOTHELIAL MIGRATION
  • LEUKOCYTE TRAFFICKING
  • ADHESION MOLECULES
  • ENDOTHELIAL-CELLS
  • T-HELPER-2 CELLS

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