In the FVB/N HER-2/<Emphasis Type="Italic">neu</Emphasis> transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by <Emphasis Type="Italic">Listeria monocytogenes</Emphasis>-based vaccines |
| |
Authors: | Reshma Singh Yvonne Paterson |
| |
Institution: | (1) Department of Microbiology, School of Medicine, University of Pennsylvania, 323 Johnson Pavilion, 36th St. and Hamilton Walk, Philadelphia, PA 19104-6076, USA |
| |
Abstract: | Listeria monocytogenes-based vaccines for HER-2/neu are capable of breaking tolerance in FVB/N rat HER-2/neu transgenic mice. The growth of implanted
NT-2 tumors, derived from a spontaneously occurring tumor in the FVB/N HER-2/neu transgenic mouse, was significantly slower
in these mice following vaccination with a series of L. monocytogenes-based vaccines for HER-2/neu. Mechanisms of T cell tolerance that exist in these transgenic mice include the absence of functional
high avidity anti-HER-2/neu CD8+ T cells and the presence of CD4+CD25+ regulatory T cells. The in vivo depletion of these regulatory T cells resulted in the slowing in growth of tumors even without
the treatment of mice with an anti-HER-2/neu vaccine. The average avidities of responsive CD8+ T cells to six of the nine epitopes in HER-2/neu we examined, four of which were identified in this study, are shown here
to be of a lower average avidity in the transgenic mice versus wild type FVB/N mice. In contrast, the average avidity of CD8+ T cells to three epitopes that showed the lowest avidity in the wild-type mice did not differ between wild type and transgenic
mice. This study demonstrates the ability of L. monocytogenes-based vaccines to impact upon tolerance to HER-2/neu in FVB/N HER-2/neu transgenic mice and further defines some of the aspects of tolerance in these mice. |
| |
Keywords: | Listeria monocytogenes CD8+ T cell epitopes HER-2/neu Tolerance Vaccines |
本文献已被 PubMed SpringerLink 等数据库收录! |
|