A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+ and CD8+ T-cell activation, protection from apoptosis, and enhanced cytokine production
| Autor: | Alicia Gómez Yafal, Linda Gritz, Jeffrey Schlom, James W. Hodge, Douglas W. Grosenbach |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
medicine.medical_treatment T cell Genetic Vectors Immunology Apoptosis CD8-Positive T-Lymphocytes Biology Lymphocyte Activation Receptors Tumor Necrosis Factor Interleukin 21 medicine Humans Cytotoxic T cell Transgenes IL-2 receptor Recombination Genetic Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Effector ZAP70 Membrane Proteins Receptors OX40 CD58 Antigens Intercellular Adhesion Molecule-1 Molecular biology Cytokine medicine.anatomical_structure Antigens Surface B7-1 Antigen Cytokines CD8 |
| Zdroj: | Cellular Immunology. 222:45-57 |
| ISSN: | 0008-8749 |
| Popis: | The role of OX40L on the activation of T cells was investigated using poxvirus vectors expressing OX40L alone or in combination with three other T-cell costimulatory molecules: B7-1, ICAM-1, and LFA-3. Poxvirus vector-infected cells were used to stimulate naive or activated CD4 + and CD8 + T cells. These studies demonstrate that (a) OX40L plays a role in sustaining the long-term proliferation of CD8 + T cells in addition to the known effect on CD4 + T cells following activation, (b) OX40L enhances the production of Th1 cytokines (IL-2, IFN-γ, and TNF-α) from both CD4 + and CD8 + while no change in IL-4 expression was observed, and (c) the anti-apoptotic effect of OX40L on T cells is likely the result of sustained expression of anti-apoptotic genes while genes involved in apoptosis are inhibited. In addition, these are the first studies to demonstrate that the combined use of a vector driving the expression of OX40L with three other costimulatory molecules (B7-1, ICAM-1, and LFA-3) both enhances initial activation and then further potentiates sustained activation of naive and effector T cells. |
| Databáze: | OpenAIRE |
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