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
Notes: Export Date: 12 September 2014 -- Molecular Sequence Numbers: GENBANK: AB019214, AB022159, AF055664, AF218069, U19604, X65553; -- Source: Scopus
Citation Impact
MSK Authors
  1. Lloyd J Old
    593 Old