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IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells
Sigrid Dubois1, Jennifer Mariner, Thomas A Waldmann
1Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
We report intriguing aspects of the contribution of IL-15Ralpha to IL-15 functions. Consistent with high-affinity interactions between IL-15 and IL-15Ralpha, these two molecules form stable complexes on the cell surface of activated monocytes. The formation of IL-15/IL-15Ralpha complexes on cell surfaces induces a trans-endosomal recycling of IL-15 leading to the persistence of surface-bound IL-15 due to the constant reappearance of IL-15 on plasma membranes. This complex contributes to the long survival of T cells expressing IL-15Ralpha after IL-15 withdrawal. Finally, these complexes on activated monocytes present IL-15 in trans to target cells such as CD8(+) T cells that express only IL-2/15Rbeta and gammac upon cell-cell interaction.
Insights
Interleukin-15 receptor alpha (IL-15Ralpha) forms stable complexes with IL-15 on monocytes, enabling IL-15 recycling and sustained T cell survival. These complexes present IL-15 to target cells, enhancing immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-15 (IL-15) is crucial for T cell development and survival.
- The IL-15 receptor complex, including IL-15Ralpha, mediates IL-15 signaling.
- Understanding IL-15Ralpha's role in IL-15 presentation is key to immune regulation.
Purpose of the Study:
- To elucidate the functional contribution of IL-15Ralpha to IL-15 functions.
- To investigate the formation and dynamics of IL-15/IL-15Ralpha complexes.
- To determine the mechanism by which these complexes influence T cell survival and target cell interaction.
Main Methods:
- Cell surface complex formation analysis.
- Trans-endosomal recycling assays.
- T cell survival studies post-IL-15 withdrawal.
- In vitro co-culture experiments with target cells.
Main Results:
- IL-15 and IL-15Ralpha form stable complexes on activated monocytes.
- These complexes undergo trans-endosomal recycling, leading to persistent surface-bound IL-15.
- IL-15/IL-15Ralpha complexes promote long-term survival of IL-15Ralpha-expressing T cells.
- Activated monocytes present IL-15 in trans to CD8(+) T cells via these complexes.
Conclusions:
- IL-15Ralpha plays a critical role in stabilizing IL-15 on cell surfaces.
- Trans-endosomal recycling of IL-15/IL-15Ralpha complexes enhances IL-15 availability and T cell persistence.
- Monocyte-presented IL-15 via these complexes facilitates trans-presentation to T cells, impacting adaptive immunity.