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Induction of Lymphocytes Cytotoxic to Oral Epithelial Cells by Streptococcus mitis Superantigen

Department of Microbiology and Immunology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan, Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan

A. Sugiyama

Department of Microbiology and Immunology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan

T. Uchiyama

Department of Microbiology and Immunology, Tokyo Woman's Medical College, Tokyo 162, Japan

H. Igarashi

Department of Microbiology, Tokyo Metropolitan Research Laboratory of Public Health, Tokyo 169, Japan

H. Ohkuni

Division of Immunology, Institute of Gerontology, Nippon Medical School, Kawasaki 211, Japan

S. Nagaoka

Department of Operative Dentistry and Endodontology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan

S. Kotani

Osaka College of Medical Technology, Osaka 530, Japan

H. Takada

Department of Microbiology and Immunology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890, Japan

The preparation of a superantigenic fraction F-2 from the culture supernatant of Streptococcus mitis 108, a fresh isolate from human tooth surfaces, was reported previously. Now, to determine the possible pathogenic role of the superantigen in oral mucosal diseases, we examined the cytotoxic effects of human peripheral blood T-cells activated with F-2 on human oral epithelial cells. T-cells activated with F-2 were cytotoxic to the human squamous carcinoma HO-l-N-1 cells derived from the oral mucosa, similar to those activated with Staphylococcus aureus enterotoxin B (SEB). This cytotoxic effect was increased in a dose-dependent manner by the addition of the respective stimulant, F-2 or SEB, to the cytotoxic assay system. F-2 endowed mainly CD8+ T-cells with cytotoxic activity. Pretreatment with human interferon gamma increased the sensitivity of the HO-l-N-1 cells to the cytotoxic effects of F-2-activated T-cells. The F-2-activated T-cells were also cytotoxic to human keratinocytes derived from gingiva. There was no correlation between the degree of cytotoxicity and the levels of tumor necrosis factor alpha in co-cultures of F-2-activated T-cells and HO-l-N-1 cells. A double-chamber plate experiment revealed no cytotoxic effects when the F-2-activated T-cells were separated from the HO-l-N-1 cells. Supernatants of the co-cultures of target and effector cells were not cytotoxic to HO-1-N-1 cells. These findings suggest that the cytotoxic effects of the F-2-activated T-cells on HO-l-N-1 cells were mediated not by soluble factors but by the direct interaction between the activated T-cells and the target cells. The cytotoxicity of the F-2-activated T-cells against HO-l-N-1 cells was markedly inhibited by monoclonal antibodies (MAbs) against CDlla and CD54, but was only slightly inhibited by MAbs against human leukocyte antigen (HLA)-DR and CD2. Thus, the interaction between lymphocyte-function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) was crucial for the F-2-dependent T-cell-mediated cytotoxicity against oral epithelial cells, while HLA-DR and CD2 molecules are not necessarily involved in the cytotoxicity observed.

Key Words: Streptococcus mitis, superantigen • cytotoxicity • ICAM-1 • LFA-1

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Journal of Dental Research, Vol. 75, No. 3, 927-934 (1996)
DOI: 10.1177/00220345960750031001


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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Matsushita, K. Articles by Takada, H. Search for Related Content PubMed PubMed Citation Articles by Matsushita, K. Articles by Takada, H. Social Bookmarking                         What's this?