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Coordinate Expression and Trans Presentation of Interleukin (IL)-15R and IL-15 Supports Natural Killer Cell and Memory CD8⁺ T Cell Homeostasis

Department of Medicine, University of California, San Francisco, San Francisco, CA 94143

Address correspondence to Averil Ma, Dept. of Medicine, University of California, San Francisco, 513 Parnassus Ave., S-1057, Box 451, San Francisco, CA 94143. Phone: (415) 502-9405; Fax: (415) 502-9404; email: ama1{at}itsa.ucsf.edu

The high affinity interleukin (IL)-15 receptor, IL-15R, is essential for supporting lymphoid homeostasis. To assess whether IL-15R's role in vivo is to trans present IL-15, we generated mixed bone marrow chimera from IL-15R– and IL-2/15Rß–deficient mice. We find that IL-15R–competent, IL-2/15Rß–deficient cells are able to support IL-15R–deficient natural killer (NK) and memory CD8⁺ T cells, thus ruling out secondary signals on these cells and demonstrating that IL-15R–mediated presentation of IL-15 in trans is the primary mechanism by which IL-15R functions in vivo. Surprisingly, using IL-15– and IL-15R–deficient mixed chimera, we also find that IL-15 and IL-15R must be expressed by the same cells to present IL-15 in trans, indicating that IL-15R is required on a cellular level for the elaboration of IL-15. These studies indicate that IL-15R defines homeostatic niches for NK and memory CD8⁺ T cells by controlling both the production and the presentation of IL-15 in trans to NK and CD8⁺ memory T cells.

Key Words: intracellular cytokine receptor • IL-15/IL-15R preassociation • mixed chimera • IL-2Rß

Abbreviation used in this paper: _c, chain.

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