Brief Definitive Report

T Cell–independent Interleukin 15R Signals Are Required for Bystander Proliferation

Correspondence to: Averil Ma, Departments of Medicine and the Ben May Institute for Cancer Research, University of Chicago, MC6084, 5841 S. Maryland Ave., Chicago, IL 60637. Tel:773-834-0687 Fax:773-702-2281 E-mail:ama{at}medicine.bsd.uchicago.edu.

Cytokine driven or "bystander" proliferation of T cells occurs in vivo independently of major histocompatibility complex–T cell receptor interactions. This process may be important for supporting T cell homeostasis and facilitating T cell responses to microbial antigens, and may involve the cytokine interleukin (IL)-15. In this study, we find that IL-15R–deficient (IL-15R^-/-) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8⁺ T cells. Surprisingly, IL-15R^-/- CD8⁺ T cells proliferate in response to poly I:C when adoptively transferred into normal mice, and normal CD8⁺ T cells fail to proliferate in IL-15R^-/- mice. Normal mice reconstituted with IL-15R^-/- bone marrow cells also fail to exhibit bystander responses. Thus, CD8⁺ T cell independent IL-15R signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8⁺ T cells proliferate in IL-15R^-/- mice after treatment with IL-15. Therefore, IL-15R signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15R supports memory phenotype CD8⁺ T cell proliferation, and suggest novel mechanisms by which memory CD8⁺ T cells are maintained in vivo.

Key Words: IL-15, lymphoid homeostasis, memory, CD8⁺ T lymphocyte, poly I:C

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