T Cell–Independent Interleukin 15rα Signals Are Required for Bystander Proliferation

• DOI: 10.1084/jem.194.8.1187
• Publication Date: 2002-07-26T16:48:33Z
• Authors: James P. Lodolce; Patrick R. Burkett; David L. Boone; Marcia Chien; Averil Ma
• Keywords: Interleukin-15; Male; Mice, Knockout; 0303 health sciences; Interferon Inducers; Receptors, Interleukin-15; Receptors, Interleukin-2; CD8-Positive T-Lymphocytes; Hematopoietic Stem Cells; Lymphocyte Activation; Adoptive Transfer; Radiation Tolerance; Killer Cells, Natural; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Poly I-C; Animals; Female; RNA, Messenger; Cell Division; Cells, Cultured

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-15Rα–deficient (IL-15Rα−/−) mice fail to undergo poly I:C or IL-15 driven bystander proliferation of CD8+ T cells. Surprisingly, IL-15Rα−/− 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-15Rα−/− mice. Normal mice reconstituted with IL-15Rα−/− bone marrow cells also fail to exhibit bystander responses. Thus, CD8+ T cell independent IL-15Rα signals from radiation sensitive hematopoietic cells are likely required for bystander responses. Moreover, normal CD8+ T cells proliferate in IL-15Rα−/− mice after treatment with IL-15. Therefore, IL-15Rα signals may mediate a positive feedback loop involving the further physiological production of IL-15. These findings provide new insights into how IL-15Rα supports memory phenotype CD8+ T cell proliferation, and suggest novel mechanisms by which memory CD8+ T cells are maintained in vivo.