Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gamma delta T cells
- Author(s)
- Street, SEA; Hayakawa, Y; Zhan, YF; Lew, AM; MacGregor, D; Jamieson, AM; Diefenbach, A; Yagita, H; Godfrey, DI; Smyth, MJ;
- Details
- Publication Year 2004-03-15,Volume 199,Issue #6,Page 879-884
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking beta-2 microglobulin (beta2m; and thus MHC class I, CD1d, and CD16) and/or perform, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perform gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked beta2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/beta2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perform, but not IFN-gamma, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1(+) and gammadeltaTCR(+) T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and gammadeltaTCP(+) T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- PORE-FORMING PROTEIN; INTERFERON-GAMMA; DEFICIENT MICE; TUMOR SURVEILLANCE; NKT CELLS; IN-VIVO; EXPRESSION; PERFORIN; METASTASIS; SUSCEPTIBILITY
- Publisher's Version
- https://doi.org/10.1084/jem.20031981
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-03-15 12:00:00