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T cell-independent interleukin 15Ralpha signals are required for bystander proliferation.
J P Lodolce1, P R Burkett, D L Boone
1Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
The Journal of Experimental Medicine
|October 17, 2001
Summary
Interleukin-15 receptor alpha (IL-15Ralpha) signals on hematopoietic cells are crucial for bystander T cell proliferation. This IL-15Ralpha signaling supports memory CD8(+) T cell maintenance in vivo.
Area of Science:
- Immunology
- Cell Biology
Background:
- Cytokine-driven T cell proliferation, independent of MHC-TCR interactions, supports immune homeostasis and responses.
- Interleukin-15 (IL-15) is implicated in this bystander proliferation process.
Purpose of the Study:
- To investigate the role of IL-15 receptor alpha (IL-15Ralpha) in T cell bystander proliferation.
- To elucidate the cellular source of IL-15Ralpha signals required for CD8(+) T cell proliferation.
Main Methods:
- Utilized IL-15Ralpha-deficient (IL-15Ralpha(-/-)) mice and adoptive transfer experiments.
- Examined CD8(+) T cell proliferation in response to poly I:C or IL-15 stimulation.
- Investigated responses in mice reconstituted with IL-15Ralpha(-/-) bone marrow cells.
Main Results:
- IL-15Ralpha(-/-) mice failed to exhibit poly I:C or IL-15 driven bystander proliferation of CD8(+) T cells.
- Adoptive transfer revealed that IL-15Ralpha signals from radiation-sensitive hematopoietic cells, not T cells themselves, are required for bystander responses.
- Normal CD8(+) T cells proliferated in IL-15Ralpha(-/-) mice upon IL-15 treatment, suggesting a feedback loop for IL-15 production.
Conclusions:
- IL-15Ralpha signaling on hematopoietic cells is essential for CD8(+) T cell bystander proliferation.
- These findings reveal novel mechanisms for memory CD8(+) T cell maintenance and proliferation in vivo.