Recruitment of IFN-γ-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 Liversidge, Peter F. Sharp, John V. Forrester, Isabel J. Crane

Research output: Contribution to journalArticle

51 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-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.

LanguageEnglish
Pages3215-3224
Number of pages10
JournalJournal of Immunology
Volume172
Issue number5
DOIs
Publication statusPublished - 1 Mar 2004

Fingerprint

Th2 Cells
Th1 Cells
P-Selectin
E-Selectin
Retina
Lymphocyte Function-Associated Antigen-1
Intercellular Adhesion Molecule-1
Autoimmune Diseases
Th1-Th2 Balance
T-Lymphocytes
Ophthalmoscopy
Venules
Adoptive Transfer
P-selectin ligand protein
Confocal Microscopy
Lasers
Up-Regulation

Keywords

  • animals
  • autoimmune diseases
  • blood-retinal barrier
  • chemotaxis, leukocyte
  • cytokines
  • e-selectin
  • endothelium, vascular
  • female
  • hyaluronan receptors
  • hyaluronic acid
  • intercellular adhesion molecule-1
  • interferon-gamma
  • ligands
  • lymphocyte function-associated antigen-1
  • membrane glycoproteins
  • mice
  • mice, inbred C57BL
  • P-selectin
  • RNA, messenger
  • retina
  • retinitis
  • Th1 cells
  • uveitis

Cite this

Xu, Heping ; Manivannan, Ayyakkannu ; Jiang, Hui-Rong ; Liversidge, Janet ; Sharp, Peter F. ; Forrester, John V. ; Crane, Isabel J. / Recruitment of IFN-γ-producing (Th1-like) cells into the inflamed retina in vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin interactions. In: Journal of Immunology . 2004 ; Vol. 172, No. 5. pp. 3215-3224.
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Recruitment of IFN-γ-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; Sharp, Peter F.; Forrester, John V.; Crane, Isabel J.

In: Journal of Immunology , Vol. 172, No. 5, 01.03.2004, p. 3215-3224.

Research output: Contribution to journalArticle

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T1 - Recruitment of IFN-γ-producing (Th1-like) cells into the inflamed retina in vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin interactions

AU - Xu, Heping

AU - Manivannan, Ayyakkannu

AU - Jiang, Hui-Rong

AU - Liversidge, Janet

AU - Sharp, Peter F.

AU - Forrester, John V.

AU - Crane, Isabel J.

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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.

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KW - autoimmune diseases

KW - blood-retinal barrier

KW - chemotaxis, leukocyte

KW - cytokines

KW - e-selectin

KW - endothelium, vascular

KW - female

KW - hyaluronan receptors

KW - hyaluronic acid

KW - intercellular adhesion molecule-1

KW - interferon-gamma

KW - ligands

KW - lymphocyte function-associated antigen-1

KW - membrane glycoproteins

KW - mice

KW - mice, inbred C57BL

KW - P-selectin

KW - RNA, messenger

KW - retina

KW - retinitis

KW - Th1 cells

KW - uveitis

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EP - 3224

JO - Journal of Immunology

T2 - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

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