title: Autoreactive and heat shock protein 60-recognizing CD4+ T-cells show antitumor activity against syngeneic fibrosarcoma.
abstract: A CD4+ heat shock protein (hsp) 60-recognizing autoreactive T-cell line (BASL1) and clone (BASL1.1) were examined for their antitumor activity against major histocompatibility complex class II- syngeneic Meth A fibrosarcoma (Meth A), which was immunofluorescently stained with monoclonal antibody specific for hsp 60. In in vitro proliferative assay, BASL1.1 was suggested to recognize Meth A-derived hsp 60 presented by syngeneic antigen-presenting cells in a major histocompatibility complex class II-restricted manner. This cell line and clone showed antitumor activity in tumor-neutralizing (Winn) assay. BASL1 and BASL1.1 cells produced gamma-interferon, tumor necrosis factor, and interleukin 2 but not interleukin 4 by the stimulation with syngeneic spleen cells. In cytolytic assay, these cell lines and clones showed neither direct nor indirect (bystander) cytolysis against Meth A. In cytostatic assay, these cells inhibited the proliferation of Meth A in the presence of syngeneic macrophages, and this activity was abrogated by the addition of anti-gamma-interferon monoclonal antibody. Recombinant gamma-interferon could induce cytostatic activity only in the presence of macrophages, and tumor necrosis factor synergized this activity. Antitumor activity induced by BASL1 was abrogated by the administration of anti-CD8 monoclonal antibody in vivo, suggesting that CD8+ cytotoxic T-lymphocytes are essential and final effector cells for BASL1-mediated Meth A rejection. These findings indicate that CD4+ autoreactive and hsp 60-recognizing T-cells show two types of antitumor activity: cytostasis and induction of tumor-specific cytotoxic T-lymphocytes. Furthermore, these results imply that tumor-specific immunity could be elicited by CD4+ helper T-cells which recognize hsp.
authors.affiliation: Department of Immunology, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Kurosawa
authors.forename: H
authors.initials: H
authors.lastname: Takimoto
authors.forename: K
authors.initials: K
authors.lastname: Nomoto
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000276:immunology* / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016827:CD8 Antigens; D002478:Cells, Cultured; D018834:Chaperonin 60; D002999:Clone Cells; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016827:CD8 Antigens; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D008748:Methylcholanthrene