期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 200, 期 7, 页码 825-834出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041389
关键词
intracellular cytokine receptor; IL-1 5/IL-15R alpha preassociation; mixed chimera; IL-2R beta
资金
- NIAID NIH HHS [R01 AI059827, R01 AI045860, R01 AI59827, R01 AI45860] Funding Source: Medline
- NIDDK NIH HHS [T32DK60414, T32 DK060414] Funding Source: Medline
The high affinity interleukin (IL)-15 receptor, IL-15Ralpha, is essential for supporting lymphoid homeostasis. To assess whether IL-15Ralpha's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15Ralpha- and IL-2/15Rbeta-deficient mice. We find that IL-15Ralpha-competent, IL-2/15Rbeta-deficient cells are able to support IL-15Ralpha-deficient natural killer (NK) and memory CD8(+) T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15Ralpha-niediated presentation of IL-15 in trans is the primary mechanism by which IL-15Ralpha functions in vivo. Surprisingly, using IL-15- and IL-15Ralpha-deficient mixed chimera, we also find that IL-15 and IL-15Ralpha must be expressed by the same cells to present IL-15 in trans, indicating that IL-15Ralpha is required oil a cellular level for the elaboration of IL-15. These studies indicate that IL-15Ralpha defines homeostatic niches for INK and memory CD8(+) T cells by controlling both the production and the presentation of IL-15 in trails to NK and CD8(+) memory T cells.
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