| First Author | Nishikawa H | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 26 | Pages | 9253-7 |
| PubMed ID | 15961541 | Mgi Jnum | J:99871 |
| Mgi Id | MGI:3584087 | Doi | 10.1073/pnas.0503852102 |
| Citation | Nishikawa H, et al. (2005) Accelerated chemically induced tumor development mediated by CD4+CD25+ regulatory T cells in wild-type hosts. Proc Natl Acad Sci U S A 102(26):9253-7 |
| abstractText | 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. |
