B-Myb overexpression results in activation and increased Fas/Fas ligand-mediated cytotoxicity of T and NK cells.
J Immunol
; 167(1): 242-9, 2001 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-11418655
ABSTRACT
The human B-myb gene encodes a transcriptional regulator that plays an important role in cell cycle progression, differentiation, and survival. To assess the in vivo role of B-myb, we investigated the phenotype of mouse transgenic lines in which B-Myb expression in lymphoid tissues was driven by the LCK proximal promoter. Overexpression of B-Myb had no measurable effect on the subsets of splenic and thymic lymphocytes, but was associated with increased expression of Fas ligand in NK and T cells. B-Myb-overexpressing splenocytes expressed higher IFN-gamma levels and contained higher percentages of cytokine-producing cells than wild-type (wt) splenocytes, as detected by Western blot analysis and ELISPOT assays, respectively. Ex vivo-cultured transgenic thymocytes and splenocytes had decreased survival compared with the corresponding cells from wt mice, possibly dependent on increased expression of Fas ligand. In addition, Fas ligand-dependent cytotoxicity of transgenic T and NK cells was significantly higher than that mediated by their wt counterparts. Together, these results indicate that B-Myb overexpression results in T and NK cell activation and increased cytotoxicity. Therefore, in addition to its well-established role in proliferation and differentiation, B-myb also appears to be involved in activation of NK and T cells and in their regulation of Fas/Fas ligand-mediated cytotoxicity
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Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Células Matadoras Naturais
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Ativação Linfocitária
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Linfócitos T Citotóxicos
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Transativadores
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Proteínas de Ciclo Celular
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Receptor fas
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Citotoxicidade Imunológica
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Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article