Increased CD8+ T Cell Memory to Concurrent Infection at the Expense of Increased Erosion of Pre-existing Memory: The Paradoxical Role of IL-15
| Autor: | Dean K. Smith, Yvan Chapdelaine, Lakshmi Krishnan, Joao A. Pedras-Vasconcelos, Subash Sad |
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| Rok vydání: | 2003 |
| Předmět: |
Ovalbumin
Lymphocyte T cell Immunology Immunization Secondary Down-Regulation Mice Transgenic CD8-Positive T-Lymphocytes Mice Adjuvants Immunologic Cell Line Tumor medicine Animals Tuberculosis Immunology and Allergy Cytotoxic T cell Listeriosis Interleukin-15 Immunity Cellular biology CD44 cell Mycobacterium bovis Peptide Fragments infection Up-Regulation Mice Inbred C57BL medicine.anatomical_structure Immunization Cell culture Interleukin 15 biology.protein role Female Immunologic Memory CD8 Plasmids |
| Zdroj: | The Journal of Immunology. 171:5454-5460 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.10.5454 |
| Popis: | The use of cytokines during vaccination, particularly IL-15, is being considered due to the unique ability of IL-15 to enhance the proliferation of memory CD8+ T cells. However, as homeostatic mechanisms limit excessive lymphocyte expansion, we addressed the consequences of this enhancement of T cell memory by IL-15. Infection of mice with either recombinant Mycobacterium bovis (BCG) expressing IL-15 (BCG-IL-15) or BCG and purified IL-15 resulted in an increased CD44, IL-2Rβ expression and increased frequency of IFN-γ-secreting CD8+ T cells. Surprisingly, the enhancement of memory to concurrent infection by IL-15 exacerbated the attrition of pre-existing memory. Infection of mice with Listeria monocytogenes expressing OVA resulted in potent OVA257–264-specific CD8+ T cell memory, and a challenge of these mice with either BCG-IL-15 or BCG and purified IL-15 resulted in an increased erosion of OVA257–264-specific CD8+ T cell memory, relative to BCG. Enhancement in the erosion of OVA-specific CD8+ T cell memory by BCG-IL-15 resulted in a consequently greater impairment in protection against a challenge with OVA-expressing tumor cells. We thus raise important questions regarding vaccinations that are aimed at maximizing T cell memory without considering the impact on pre-existing T cell memory. |
| Databáze: | OpenAIRE |
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