Journal of Dental Research, Vol 75, 927-934, Copyright © 1996 by International & American Associations for Dental Research Online Journals
Induction of lymphocytes cytotoxic to oral epithelial cells by Streptococcus mitis superantigen
K. Matsushita, A. Sugiyama, T. Uchiyama, H. Igarashi, H. Ohkuni, S. Nagaoka, S. Kotani and H. Takada
Department of Microbiology and Immunology, Kagoshima University Dental School, 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-1-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-1-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-1-N-1 cells. A double-chamber plate experiment
revealed no cytotoxic effects when the F-2-activated T-cells were separated
from the HO-1-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-1-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-1-N-1 cells was markedly inhibited by
monoclonal antibodies (MAbs) against CD11a 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.
