CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer
| Autor: | Masoud H. Manjili, Hooman Nikizad, Mehran Habibi, Madhu Gowda, Andrea Worschech, Amy Depcrynski, Francesco M. Marincola, Ena Wang, Shawn E. Holt, Maciej Kmieciak, Kamar Godder |
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| Rok vydání: | 2010 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Cell Survival Receptor ErbB-2 CASP8 and FADD-Like Apoptosis Regulating Protein Priming (immunology) CD8-Positive T-Lymphocytes Article TNF-Related Apoptosis-Inducing Ligand Interleukin 21 Interferon-gamma Mice Cross-Priming Cytotoxic T cell Animals IL-2 receptor Antigen-presenting cell CD40 biology Gene Expression Profiling Mammary Neoplasms Experimental Telomere Natural killer T cell Xenograft Model Antitumor Assays Coculture Techniques Tumor Burden Hyaluronan Receptors Phenotype Oncology Gene Expression Regulation Immunology biology.protein Interleukin 12 Female |
| Zdroj: | Breast cancer research and treatment. 126(2) |
| ISSN: | 1573-7217 |
| Popis: | 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 neu-positive 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. |
| Databáze: | OpenAIRE |
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