Transregulation of memory CD8 T-cell proliferation by IL-15Ralpha+ bone marrow-derived cells

Area of Science:

• Immunology
• Cell Biology
• T cell biology

Background:

• Interleukin 15 (IL-15) and its receptor alpha (IL-15Ralpha) are essential for memory CD8 T cell proliferation.
• The specific cell types responsible for expressing IL-15 and IL-15Ralpha in mediating this proliferation remain unclear.

Purpose of the Study:

• To identify the cellular sources of IL-15 and IL-15Ralpha critical for memory CD8 T cell proliferation.
• To elucidate the mechanisms of IL-15 mediated T cell division.

Main Methods:

• Bone marrow (BM) chimeras and mixed BM chimeras were utilized to track cell-specific expression.
• In vivo cell transfer experiments were performed using wild-type and IL-15Ralpha knockout mice.
• Analysis of CD8 T cell proliferation in different organs (spleen, lung) was conducted.

Main Results:

• Virus-specific CD8 memory T cell proliferation was driven by IL-15 from either BM-derived or parenchymal cells.
• IL-15Ralpha expression on memory CD8 T cells was not required for their proliferation.
• IL-15Ralpha-expressing BM-derived cells were critical for T cell division in the spleen, while both BM-derived and parenchymal cells contributed in the lung.
• Soluble IL-15 proliferation required IL-15Ralpha on opposing cells and IL-15Rbeta on CD8 memory T cells.

Conclusions:

• Transpresentation of IL-15 by IL-15Ralpha on BM-derived cells is the primary mechanism for basal memory CD8 T cell proliferation.
• Cellular context (spleen vs. lung) influences the contribution of different cell types to T cell proliferation.
• IL-15 directly interacts with CD8 memory T cells via IL-15Rbeta for proliferation.