CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses Journal Article
| Authors: | Nishikawa, H.; Kato, T.; Tanida, K.; Hiasa, A.; Tawara, I.; Ikeda, H.; Ikarashi, Y.; Wakasugi, H.; Kronenberg, M.; Nakayama, T.; Taniguchi, M.; Kuribayashi, K.; Old, L. J.; Shiku, H. |
| Article 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 α-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 Jα281 -/- 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. |
| Keywords: | controlled study; unclassified drug; nonhuman; cd8 antigen; antigen expression; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; cancer susceptibility; lung neoplasms; animal experiment; animal model; tumor antigen; mice, inbred balb c; animalia; molecular cloning; lung metastasis; cellular immunity; immune response; nucleotide sequence; cytotoxic t lymphocyte; neoplasms, experimental; autoantigen; autoantigens; natural killer cell; adoptive transfer; tumor immunity; cd4 antigen; tumor growth; homeostasis; antigens, cd4; genetic code; serology; tetramer; plasmid dna; immunization; interleukin 2 receptor; metastasis inhibition; gene gun; female; priority journal; article; dna j like 2 antigen |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 100 |
| Issue: | 19 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2003-09-16 |
| Start Page: | 10902 |
| End Page: | 10906 |
| Language: | English |
| DOI: | 10.1073/pnas.1834479100 |
| PUBMED: | 12947044 |
| PROVIDER: | scopus |
| PMCID: | PMC196900 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Molecular Sequence Numbers: GENBANK: AB019214, AB022159, AF055664, AF218069, U19604, X65553; -- Source: Scopus |
