In the FVB/N HER-2/neu transgenic mouse both peripheral and central tolerance limit the immune response targeting HER-2/neu induced by Listeria monocytogenes-based vaccines.

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.

• Authors: Reshma Singh, Yvonne Paterson
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 56 Issue 6 Pg. 927-38 (Jun 2007) ISSN: 0340-7004 [Print] Germany
• PMID: 17131121 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Receptor, ErbB-2

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Genetic Vectors
• Immune Tolerance
• Listeria monocytogenes (genetics)
• Mammary Neoplasms, Experimental (immunology, therapy)
• Mice
• Mice, Transgenic
• Receptor, ErbB-2 (immunology)