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Brief Definitive Report |
Signals Are Required for Bystander Proliferation
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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