First Author | Hodes RJ | Year | 1993 |
Journal | J Immunol | Volume | 150 |
Issue | 4 | Pages | 1422-8 |
PubMed ID | 8094408 | Mgi Jnum | J:3937 |
Mgi Id | MGI:52442 | Doi | 10.4049/jimmunol.150.4.1422 |
Citation | Hodes RJ, et al. (1993) Association of a V beta 2-specific superantigen with a tumorigenic milk-borne mouse mammary tumor virus. J Immunol 150(4):1422-8 |
abstractText | A number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigens that have the property of stimulating mature T lymphocytes in a TCR V beta-specific fashion and of mediating V beta-specific clonal deletion in developing T cells. The tumorigenic milk-borne MMTV carried by C3H and GR mice also have superantigen properties in vivo, and it has been proposed that this superantigenic function is critical to the infectivity and/or tumorigenicity of the virus. To test the requirement for superantigen properties in tumorigenic MMTV, a highly tumorigenic strain of MMTV isolated from BALB/c mice (BALB/cV virus) was analyzed for its effect on TCR V beta expression. It was found that exposure of newborn mice to milk-borne virus results in marked deletion of V beta 2-expressing CD4+ peripheral T cells. This deletion is detected in mature TCRhigh thymocytes as well as in peripheral T cells from virus-exposed mice. Deletion is dependent on expression of a permissive MHC type in mice exposed to virus. Subcutaneous injection of adult mice with virus-containing milk induces a substantial increase in V beta 2+ CD4+ cells in draining lymph nodes within 4 days. Thus, tumorigenic BALB/cV is associated with V beta 2-specific superantigen activity capable of mediating both T cell expansion and clonal deletion in vivo. These findings are consistent with a critical role of superantigen-mediated T cell activation in MMTV infection and tumorigenesis. |