CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Maciej Kmieciak Andrea Worschech Hooman Nikizad Madhu Gowda Mehran Habibi Amy Depcrynski Ena Wang Kamar Godder Shawn E. Holt Frances
- چاپ و سال / کشور: 2010
Description
Studies conducted in animal model of infectious diseases or H-Y antigen model suggest a crucial role for CD4? T cells in providing help for CD8? T-cell memory responses. This concept suggests that inclusion of T helper epitopes in vaccine formulation will result in improved CD8? T-cell responses. Although this concept has been applied to cancer vaccine design, the role of CD4?T cells in the memory differentiation of CD8? T cells and retention of their anti-tumor function have never been tested in breast cancer model. Using the FVB mouse model of neupositive breast carcinoma we report for the first time that helpless T cells showed cytostatic or tumor inhibitory effects during primary tumor challenge whereas, helped T cells showed cytotoxic effects and resulted in complete tumor rejection. Such differential effects, in vivo, were associated with higher frequency of CD8?PD-L1? and CD8?PD-1? T cells in animals harboring helpless T cells as well as higher titer of IL-2 in the sera of animals harboring helped T cells. However, depletion of CD4? T cells did not alter the ability of neu-specific CD8? T cells to differentiate into memory cells and to retain their effector function against the tumor during recall challenge. These results suggest the inhibitory role of CD4? T cells on CD8? T-cell exhaustion without substantial effects on the differentiation of memory T cells during priming phase of the immune responses against breast cancer.
Breast Cancer Res Treat (2011) 126:385–394 DOI 10.1007/s10549-010-0942-8 Received: 22 February 2010 / Accepted: 6 May 2010 / Published online: 18 May 2010 Springer Science+Business Media, LLC. 2010
