CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses.
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.
Nishikawa
Hiroyoshi
H
Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan.
Kato
Takuma
T
Tanida
Koji
K
Hiasa
Atsunori
A
Tawara
Isao
I
Ikeda
Hiroaki
H
Ikarashi
Yoshinori
Y
Wakasugi
Hiro
H
Kronenberg
Mitchell
M
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Kuribayashi
Kagemasa
K
Old
Lloyd J
LJ
Shiku
Hiroshi
H
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*
D001324:Autoantigens; D015704:CD4 Antigens