title: Suppression of an already established tumor growing through activated mucosal CTLs induced by oral administration of tumor antigen with cholera toxin.
abstract: Priming of CTLs at mucosal sites, where various tumors are originated, seems critical for controlling tumors. In the present study, the effect of the oral administration of OVA plus adjuvant cholera toxin (CT) on the induction of Ag-specific mucosal CTLs as well as their effect on tumor regression was investigated. Although OVA-specific TCRs expressing lymphocytes requiring in vitro restimulation to gain specific cytotoxicity could be detected by OVA peptide-bearing tetramers in both freshly isolated intraepithelial lymphocytes and spleen cells when OVA was orally administered CT, those showing direct cytotoxic activity without requiring in vitro restimulation were dominantly observed in intraepithelial lymphocytes. The magnitude of such direct cytotoxicity at mucosal sites was drastically enhanced after the second oral administration of OVA with intact whole CT but not with its subcomponent, an A subunit (CTA) or a B subunit (CTB). When OVA plus CT were orally administrated to C57BL/6 mice bearing OVA-expressing syngeneic tumor cells, E.G7-OVA, in either gastric tissue or the dermis, tumor growth was significantly suppressed after the second oral treatment; however, s.c. or i.p. injection of OVA plus CT did not show any remarkable suppression. Those mucosal OVA-specific CTLs having direct cytotoxicity expressed CD8alphabeta but not CD8alphaalpha, suggesting that they originated from thymus-educated cells. Moreover, the infiltration of such OVA-specific CD8(+) CTLs was observed in suppressed tumor tissues. These results indicate that the growth of ongoing tumor cells can be suppressed by activated CD8alphabeta CTLs with tumor-specific cytotoxicity via an orally administered tumor Ag with a suitable mucosal adjuvant.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Wakabayashi
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Keiichi
authors.initials: K
authors.lastname: Moriya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D016827:CD8 Antigens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D010047:Ovalbumin; D002772:Cholera Toxin