RT Journal Article
SR Electronic
T1 B-Myb Overexpression Results in Activation and Increased Fas/Fas Ligand-Mediated Cytotoxicity of T and NK Cells
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 242
OP 249
DO 10.4049/jimmunol.167.1.242
VO 167
IS 1
A1 Powzaniuk, Mark A.
A1 Trotta, Rossana
A1 Loza, Matthew J.
A1 Harth, Amy
A1 Iozzo, Renato V.
A1 Eisenlohr, Lawrence C.
A1 Perussia, Bice
A1 Calabretta, Bruno
YR 2001
UL http://www.jimmunol.org/content/167/1/242.abstract
AB 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-γ 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