Cooperation of Human Tumor-Reactive CD4+ and CD8+ T Cells after Redirection of Their Specificity by a High-Affinity p53A2.1-Specific TCR
| Autor: | Jürgen Kuball, Linda A. Sherman, Matthias Theobald, Renate Engel, Edite Antunes Ferreira, Pedro Romero, Ralf-Holger Voss, Frank Schmitz, Philippe Guillaume, Susanne Strand, Christoph Huber |
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| Rok vydání: | 2005 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Immunology Receptors Antigen T-Cell Mice Transgenic T-Cell Antigen Receptor Specificity CD8-Positive T-Lymphocytes Biology Mice Interleukin 21 Transduction Genetic Tumor Cells Cultured medicine Animals Humans Immunology and Allergy Cytotoxic T cell Cloning Molecular Antigen-presenting cell T-cell receptor Flow Cytometry Natural killer T cell Cell biology CTL Infectious Diseases medicine.anatomical_structure Tumor Suppressor Protein p53 CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Immunity. 22:117-129 |
| ISSN: | 1074-7613 |
| Popis: | Efficient immune attack of malignant disease requires the concerted action of both CD8 + CTL and CD4 + Th cells. We used human leukocyte antigen (HLA)-A*0201 (A2.1) transgenic mice, in which the mouse CD8 molecule cannot efficiently interact with the α3 domain of A2.1, to generate a high-affinity, CD8-independent T cell receptor (TCR) specific for a commonly expressed, tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the human p53 tumor suppressor protein. Retroviral expression of this CD8-independent, p53-specific TCR into human T cells imparted the CD8 + T lymphocytes with broad tumor-specific CTL activity and turned CD4 + T cells into potent tumor-reactive, p53A2.1-specific Th cells. Both T cell subsets were cooperative and interacted synergistically with dendritic cell intermediates and tumor targets. The intentional redirection of both CD4 + Th cells and CD8 + CTL by the same high-affinity, CD8-independent, tumor-specific TCR could provide the basis for novel broad-spectrum cancer immunotherapeutics. |
| Databáze: | OpenAIRE |
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