title: CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses.
abstract: A variety of tumor-derived antigens have been defined by IgG antibodies in tumor bearers' sera with serological identification of antigens by recombinant expression cloning (SEREX), a serological expression cloning method. The majority of these antigens show no structural abnormality and seem to be wild-type autoantigens. Coimmunization with DNA encoding these autoantigens and tumor-specific cytotoxic T lymphocytes epitopes heightened CD8+ T cell responses and increased resistance to tumor challenge in a CD4+ T cell-dependent manner. In contrast, immunization with these SEREX-defined autoantigens alone leads to heightened susceptibility to tumor challenge. This suppressive effect of immunization is mediated by CD4+ CD25+ T cells. In mice immunized with one of the SEREX-defined autoantigens, Dna J-like 2, the number of alpha-GalCer/CD1d tetramer+ CD3+ T cells [representing natural killer T (NKT) cells] was reduced in the pulmonary compartment, whereas no evident change in the number of other T cell subsets was observed. Experiments with Jalpha281-/- mice lacking most NKT cells indicate that NKT cells are primarily responsible for metastasis suppression and that their activity is inhibited by immunization with Dna J-like 2. We propose that SEREX identifies a pool of autoantigens that maintains and regulates immunological homeostasis via CD4+ CD25+ regulatory T cells.
authors.affiliation: Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
authors.forename: Koji
authors.initials: K
authors.lastname: Tanida
authors.forename: Atsunori
authors.initials: A
authors.lastname: Hiasa
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kagemasa
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D015704:CD4 Antigens