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 t...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-09, Vol.100 (19), p.10902-10906
Main Authors: Nishikawa, Hiroyoshi, Kato, Takuma, Tanida, Koji, Hiasa, Atsunori, Tawara, Isao, Ikeda, Hiroaki, Ikarashi, Yoshinori, Wakasugi, Hiro, Kronenberg, Mitchell, Nakayama, Toshinori, Taniguchi, Masaru, Kuribayashi, Kagemasa, Old, Lloyd J., Shiku, Hiroshi
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Antigens
Autoantigens
Autoantigens - immunology
Biological Sciences
CD4 Antigens - immunology
Cellular immunity
Female
Immunization
Immunology
Lung Neoplasms - secondary
Metastasis
Mice
Mice, Inbred BALB C
Natural killer T cells
Neoplasms, Experimental - immunology
Nodules
Plasmids
T cell receptors
T lymphocytes
T-Lymphocytes - immunology
Tumors
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Summary: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 Jα 281-/-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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1834479100