Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigen that have the ability to stimulate T cells with a certain T cell receptor (TCR) beta-chain variable region (V beta) and to mediate the V beta-specific clonal deletion. The tumorigenic milk-borne MMTV carried by C3H and GR mice also have superantigenic properties in vivo. In the present study we identified and characterized a novel V beta 8.2-specific superantigen of exogenous MMTV carried by FM mice. The open reading frame (ORF) in the 3' long terminal repeat of the MMTV was cloned by polymerase chain reaction with primers corresponding to conserved regions spanning the ORF coding region. Sequence analysis of the ORF revealed that there is no sequence identical to those in other known MMTV in the carboxy terminus implicated in TCR V beta recognition. Subcutaneous injection of the virus into adult BALB/c mice induced an approximately three- to fourfold enlargement of draining lymph nodes and a substantial increase of V beta 8.2+ CD4+ T cells in the lymph nodes within 6 days. The exposure of newborn BALB/c mice to the virus by foster nursing resulted in a marked deletion of V beta 8.2+ cells both in CD4+ and CD8+ T cells. Thus, a novel milk-borne MMTV in FM mice expresses strong superantigenic properties capable of stimulating V beta 8.2+ T cells. V beta 8.2+ T cells have been demonstrated to be frequently involved in recognition of conventional antigens and responsible for autoimmune diseases such as experimental allergic encephalomyelitis. Therefore, the MMTV (FM) may provide a new mouse model system for inducing immunodeficiency or autoimmune disease by retroviral infection.
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PMID:A V beta 8.2-specific superantigen from exogenous mouse mammary tumor virus carried by FM mice. 791 38

We previously identified a superantigen from the exogenous mouse mammary tumor virus carried by FM mice [MMTV (FM)], which can preferentially activate V beta 8.2+ CD4+ T cells by subcutaneous injection. In the present study we investigated the effect of neonatal infection with the virus on the T cell receptor (TCR) beta-chain variable region (V beta) repertoire, T cell immune response, and development of experimental allergic encephalomyelitis (EAE). The infection, surprisingly, resulted in deletion of a large portion of CD4+ T cells including V beta 2+, 6+, 8.1+, 8.3+, and 14+ CD4+ T cells in addition to V beta 8.2+ CD4+ T cells. Nevertheless, the infection marginally affected T cell immune response to various antigens such as ovalbumin (OVA) and alloantigen except the abrogated response to anti-V beta 8.2 antibody-mediated receptor cross-linking. Moreover, the infection exerted a protective effect on the development of EAE in (PL/J x SJL)F1 mice. Thus, MMTV (FM) superantigen has the ability to delete a large portion of CD4+ T cells with broad TCR V beta specificity, including V beta 8.2+ CD4+ T cells, and may have potential as a therapeutic agent against autoimmune diseases.
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PMID:Deletion of CD4+ T cells by mouse mammary tumor virus (FM) superantigen with broad specificity of T cell receptor beta-chain variable region. 880 76

We have shown recently that cDNA vaccination, using a virtual lymph node, ameliorates experimental allergic encephalomyelitis. Successful cure from mammary tumor requires resolution of local tumor growth and metastases. We have examined whether targeting of CD44 cell surface adhesion molecule by cDNA vaccination plays a role in resolving mammary tumor development. We show here that CD44 cDNA vaccination decreases the tumor mass and metastatic potential in experimental mammary tumor of BALB/c mice. Vaccination of mice, inoculated with the mammary tumors, by cDNA of CD44 variant (CD44v) but not by cDNA of standard CD44, markedly reduced local tumor development and lung metastasis. Concomitantly, transfection of CD44 antisense into a highly metastatic mammary tumor cell line disrupted the CD44 expression of the cells and reduced their ability to establish local tumors as well as metastatic colonies in the lung. Moreover, when CD44v, but not standard CD44 sense cDNA, was transfected into the poorly metastatic cell line, tumor development was markedly enhanced. It is possible therefore that DNA vaccination with a specific CD44v construct could induce an immune resistance to mammary tumor progression.
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PMID:DNA vaccination with CD44 variant isoform reduces mammary tumor local growth and lung metastasis. 1856 32