| Autor: |
Nishikawa H; Second Department of Internal Medicine and Department of Bioregulation, Mie University School of Medicine, Mie 514-8507, Japan., Kato T, Tawara I, Takemitsu T, Saito K, Wang L, Ikarashi Y, Wakasugi H, Nakayama T, Taniguchi M, Kuribayashi K, Old LJ, Shiku H |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Jun 28; Vol. 102 (26), pp. 9253-7. Date of Electronic Publication: 2005 Jun 16. |
| DOI: |
10.1073/pnas.0503852102 |
| Abstrakt: |
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 Jalpha281-/- 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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