Accelerated chemically induced tumor development mediated by CD4 +CD25+ regulatory T cells in wild-type hosts Journal Article
| Authors: | Nishikawa, H.; Kato, T.; Tawara, I.; Takemitsu, T.; Saito, K.; Wang, L.; Ikarashi, Y.; Wakasugi, H.; Nakayama, T.; Taniguchi, M.; Kuribayashi, K.; Old, L. J.; Shiku, H. |
| Article Title: | Accelerated chemically induced tumor development mediated by CD4 +CD25+ regulatory T cells in wild-type hosts |
| Abstract: | We examined the role of CD4+CD25+ regulatory T cells in the development of 3-methylcholanthrene (MCA)-induced tumors. Immunization of wild-type BALB/c mice with a series of SEREX (serological identification of antigens by recombinant expression cloning)-defined broadly expressed self-antigens results in the development of highly active CD4 +CD25+ regulatory T cells. Accelerated tumor development was observed in mice immunized with self-antigens and was abolished by antibody-mediated depletion of CD4+ T cells or CD25+ T cells. A similar acceleration of tumorigenesis was also observed in mice adoptively transferred 2 or 4 weeks after MCA injection with CD4 +CD25+ T cells derived from mice immunized with DnaJ-like 2, one of these self-antigens. Experiments with Jα281-/- mice lacking invariant natural killer (iNK) T cells indicated that iNK T cells, known for their protective role in the development of MCA-induced tumors, were suppressed in immunized hosts. NK cells, also known to play a protective role in MCA induced-tumorigenesis, were also suppressed in mice immunized with serologically defined self-antigens in a CD4+CD25+ T cell-dependent manner. We propose that CD4+CD25+ regulatory T cells generated by immunization with these self-antigens enhance susceptibility to MCA induced-tumorigenesis by down-regulating iNK T and NK reactivity, and suggest that these observations provide direct evidence for the existence of cancer immunosurveillance in this system of chemical carcinogenesis. © 2005 by The National Academy of Sciences of the USA. |
| Keywords: | adolescent; unclassified drug; nonhuman; neoplasms; cell proliferation; t-lymphocytes; mouse; animals; mice; cancer susceptibility; genetic predisposition to disease; animal model; protein binding; down-regulation; wild type; mice, inbred balb c; time factors; mice, transgenic; cloning, molecular; nucleotide sequence; cd4-positive t-lymphocytes; recombinant proteins; autoantigen; natural killer cell; adoptive transfer; killer cells, natural; plasmids; cd4 antigen; mouse strain; immune deficiency; immunosurveillance; antigens, cd4; t lymphocyte subpopulation; lymphocyte depletion; interleukin 2 receptor alpha; host; immunization; carcinogens; cloning; receptors, interleukin-2; chemical compound; antigens, cd1; galactosylceramides; methylcholanthrene; 3 methylcholanthrene; self-antigen immunization; dnaj like protein; protein dnaj; antibody dependent lymphocytotoxicity; chemical carcinogenesis; serological identification of antigens by recombinant expression cloning; chromium radioisotopes |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 26 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-06-28 |
| Start Page: | 9253 |
| End Page: | 9257 |
| Language: | English |
| DOI: | 10.1073/pnas.0503852102 |
| PUBMED: | 15961541 |
| PROVIDER: | scopus |
| PMCID: | PMC1166632 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 67" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Molecular Sequence Numbers: GENBANK: AB019214, AB022159, AF055664, AF218069, D78645, U19604, U50383, X65553, XM_008348;" - "Source: Scopus" |
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