Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease

Yoko Ogawa, Masataka Kuwana, Kazuto Yamazaki, Yukihiko Mashima, Masakazu Yamada, Takehiko Mori, Shinichiro Okamoto, Yoshihisa Oguchi, Yutaka Kawakami

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

PURPOSE. To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS. Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sjögren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS. CD4+ and CD8+ T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4+ and CD8+ T cells expressed the activation marker CD154. In addition, CD4+ and CD8+ T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8+ T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS. The results strongly suggest that CD4+ and CD8+ T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.

Original languageEnglish
Pages (from-to)1888-1896
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number5
DOIs
Publication statusPublished - 2003 May 1

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Lacrimal Apparatus
Graft vs Host Disease
T-Lymphocytes
Fibroblasts
HLA-DR Antigens
Epithelial Cells
Antigen Presentation
Antigen-Presenting Cells
Transmission Electron Microscopy
Electron Microscopy
Epithelium
Macrophages
Lymphocytes
Biopsy
Antibodies

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease. / Ogawa, Yoko; Kuwana, Masataka; Yamazaki, Kazuto; Mashima, Yukihiko; Yamada, Masakazu; Mori, Takehiko; Okamoto, Shinichiro; Oguchi, Yoshihisa; Kawakami, Yutaka.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 5, 01.05.2003, p. 1888-1896.

Research output: Contribution to journalArticle

Ogawa, Yoko ; Kuwana, Masataka ; Yamazaki, Kazuto ; Mashima, Yukihiko ; Yamada, Masakazu ; Mori, Takehiko ; Okamoto, Shinichiro ; Oguchi, Yoshihisa ; Kawakami, Yutaka. / Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 5. pp. 1888-1896.
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T1 - Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease

AU - Ogawa, Yoko

AU - Kuwana, Masataka

AU - Yamazaki, Kazuto

AU - Mashima, Yukihiko

AU - Yamada, Masakazu

AU - Mori, Takehiko

AU - Okamoto, Shinichiro

AU - Oguchi, Yoshihisa

AU - Kawakami, Yutaka

PY - 2003/5/1

Y1 - 2003/5/1

N2 - PURPOSE. To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS. Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sjögren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS. CD4+ and CD8+ T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4+ and CD8+ T cells expressed the activation marker CD154. In addition, CD4+ and CD8+ T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8+ T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS. The results strongly suggest that CD4+ and CD8+ T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.

AB - PURPOSE. To examine immune processes in the lacrimal gland of patients with chronic graft-versus-host disease (cGVHD) by evaluating the expression of surface molecules associated with T-cell activation. METHODS. Antibodies to CD4, CD8, CD34, CD40, CD54, CD80, CD86, CD154, and HLA-DR were used for immunohistochemical analysis of lacrimal gland biopsy specimens obtained from nine patients with cGVHD and five with Sjögren's syndrome (SS). The regions of interest were further assessed by transmission electron microscopy. RESULTS. CD4+ and CD8+ T cells were mainly detected in the periductal areas of the glands of patients with cGVHD, but were distributed throughout the acinar areas in patients with SS. In the periductal areas of patients with cGVHD, a subpopulation of CD4+ and CD8+ T cells expressed the activation marker CD154. In addition, CD4+ and CD8+ T cells were colocalized with mononuclear infiltrates and stromal fibroblasts expressing the full component of surface molecules necessary for antigen presentation, including HLA-DR, CD54, CD40, CD80, and CD86. Electron microscopy revealed activated fibroblasts that embraced lymphocytes and macrophages with their processes. Also, there were more CD8+ T cells in the glandular epithelia of patients with cGVHD than in those with SS. Intraepithelial T cells were attached to epithelial cells by several primitive contacts and colocalized with dead cells. CONCLUSIONS. The results strongly suggest that CD4+ and CD8+ T cells in the lacrimal glands of patients with cGVHD are primarily activated in the periductal area through antigenic stimulation by potent antigen-presenting cells and stromal fibroblasts, and exert various effector functions, including cytotoxic effects on glandular epithelial cells.

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