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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.

SUBMITTER: Nishikawa H 

PROVIDER: S-EPMC196900 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses.

Nishikawa Hiroyoshi H   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  

Proceedings of the National Academy of Sciences of the United States of America 20030828 19


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 chall  ...[more]

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