Interleukin-15 mediates protection against experimental tuberculosis: A role for NKG2D-dependent effector mechanisms of CD8+ T cells
| Autor: | Manuela Heßmann, Alexandra Rausch, Christoph Hölscher, Silvia Bulfone-Paus, Alexandra Hölscher, Stefan Ehlers, Tanja Schreiber |
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| Rok vydání: | 2006 |
| Předmět: |
Interleukin-15
T cell ZAP70 Immunology CD8-Positive T-Lymphocytes Biology Natural killer T cell NKG2D Cell biology Mice Inbred C57BL Interferon-gamma Mice Interleukin 21 medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K medicine Animals Receptors Natural Killer Cell Tuberculosis Immunology and Allergy Cytotoxic T cell Female IL-2 receptor Receptors Immunologic Antigen-presenting cell |
| Zdroj: | European Journal of Immunology. 36:1156-1167 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.200535290 |
| Popis: | CD8+ T cells are involved in protection against Mycobacterium tuberculosis infection and represent a promising target for new vaccine strategies. Because IL-15 is important for the homeostasis of CD8+ T cells, we studied the immune response in IL-15-deficient mice during tuberculosis. In the absence of IL-15, CD8+ T cells failed to efficiently accumulate in draining lymph nodes and at the site of infection. The expression of antigen-specific effector functions, such as the production of interferon-gamma and cytotoxicity, were impaired in CD8+ T cells, but not CD4+ T cells, from IL-15-deficient mice. This defect was associated with an increased mortality of IL-15-deficient mice during the chronic phase of infection. The lectin-like stimulatory receptor natural killer group 2D (NKG2D) was up-regulated on CD8+ T cells only from wild-type mice, but not from IL-15-deficient mice. Mechanistically, blocking NKG2D function with an mAb inhibited M. tuberculosis-directed CD8+ T cell responses in vitro. We conclude that in addition to regulating the expansion of CD8+ T cells, IL-15 is also necessary for inducing effector mechanisms in CD8+ T cells that depend on NKG2D expression. Hence, our results implicate IL-15 and NKG2D as promising targets for modulating CD8+ T cell-mediated protection against tuberculosis. |
| Databáze: | OpenAIRE |
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