T cell-related costimulatory molecules in the conjunctiva of patients with severe allergic conjunctivitis.
BACKGROUND
We showed previously that costimulatory molecules such as OX40 and 4-1BB participate in the development of murine allergic conjunctivitis (AC). We investigated whether these molecules are expressed in the conjunctiva of patients with severe AC.


METHODS
Giant papillae were collected from 4 patients with severe AC. As a control, bulbar conjunctivas from 4 normal volunteers were used. Frozen sections of the conjunctivas were stained with anti-CD4, anti-CD8, anti-OX40, anti-4-1BB, or control antibodies (Abs) and then incubated with the biotinylated secondary Ab. Alternatively, staining was performed with a biotinylated anti inducible costimulator (ICOS) Ab. After using an avidin-biotin complex kit, the staining levels were graded from 0 to 3. For immunofluorescence analysis, conjunctival sections were stained with primary Abs that had been fluorescently labeled.


RESULTS
The conjunctival stroma of all 4 patients with severe AC were infiltrated with CD4+ and CD8+ cells, whereas only 1 control sample contained stromal CD4+ and CD8+ cells. Conjunctivas from patients but none of the control conjunctivas expressed OX40, 4-1BB, and ICOS. The expression levels of these molecules were significantly higher in patients than the control volunteers. Immunofluorescence analysis demonstrated that the OX40 and 4-1BB, but not the ICOS, molecules were expressed by the infiltrating CD4+ and/or CD8+ cells.


CONCLUSIONS
Together with the data in murine AC, OX40 and 4-1BB are expressed in the conjunctiva of patients with severe AC but not in the control conjunctivas, which suggests that OX40 and 4-1BB participate, at least in part, in the development of severe AC.
Sumi
Tamaki
T
Department of Ophthalmology and Visual Science, Kochi Medical School, Nankoku-city, Kochi, Japan.
Ishida
Waka
W
Ebihara
Nobuyuki
N
Fukushima
Atsuki
A
D053330:4-1BB Ligand / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D003228:Conjunctiva / Q000378:metabolism*; D003233:Conjunctivitis, Allergic / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D060889:Inducible T-Cell Co-Stimulator Protein; D008297:Male; D008875:Middle Aged; D053278:OX40 Ligand / Q000378:metabolism*; D055815:Young Adult
D053330:4-1BB Ligand; D000945:Antigens, Differentiation, T-Lymphocyte; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D053278:OX40 Ligand; C089251:TNFSF4 protein, human