Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease.
OBJECTIVE
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.
Ogawa
Yoko
Y
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Kuwana
Masataka
M
Yamazaki
Kazuto
K
Mashima
Yukihiko
Y
Yamada
Masakazu
M
Mori
Takehiko
T
Okamoto
Shinichiro
S
Oguchi
Yoshihisa
Y
Kawakami
Yutaka
Y
D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006086:Graft vs Host Disease / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000276:immunology
D015703:Antigens, CD; D006684:HLA-DR Antigens