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 journalArticle

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

Cite this

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

In: The Journal of Immunology, Vol. 172, No. 5, 03.2004, p. 3215-3224.

Research output: Contribution to journalArticle

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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.",
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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AU - Xu, Heping

AU - Manivannan, Ayyakkannu

AU - Jiang, Hui-Rong

AU - Liversidge, Janet Mary

AU - Sharp, Peter Frederick

AU - Forrester, John Vincent

AU - Crane, Isabel Joan

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N2 - 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.

AB - 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.

KW - EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

KW - DIABETIC NOD MICE

KW - TH2 CELLS

KW - T-CELLS

KW - TRANSENDOTHELIAL MIGRATION

KW - LEUKOCYTE TRAFFICKING

KW - ADHESION MOLECULES

KW - ENDOTHELIAL-CELLS

KW - T-HELPER-2 CELLS

M3 - Article

VL - 172

SP - 3215

EP - 3224

JO - The Journal of Immunology

JF - The Journal of Immunology

SN - 0022-1767

IS - 5

ER -