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Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells

Todd C. Becker¹, E. John Wherry¹, David Boone³, Kaja Murali-Krishna¹, Rustom Antia², Averil Ma³ and Rafi Ahmed¹

¹ Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322
² Department of Biology, Emory University School of Medicine, Atlanta, GA 30322
³ Department of Medicine, University of Chicago, Chicago, IL 60637

Address correspondence to R. Ahmed, Emory Vaccine Center, G211 Rollins Research Bldg., 1510 Clinton Rd., Atlanta, GA 30322. Phone: 404-727-4700; Fax: 404-727-3722; E-mail: ra{at}microbio.emory.edu

The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the generation and maintenance of virus-specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor chain. Both cytokine- and receptor-deficient mice made potent primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV), effectively cleared the virus and generated a pool of antigen-specific memory CD8 T cells that were phenotypically and functionally similar to memory CD8 T cells present in IL-15^+/+ mice. However, longitudinal analysis revealed a slow attrition of virus-specific memory CD8 T cells in the absence of IL-15 signals.This loss of CD8 T cells was due to a severe defect in the proliferative renewal of antigen-specific memory CD8 T cells in IL-15^-/- mice. Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.

Key Words: CD8 T cell • immunological memory • IL-15 • homeostasis • viral immunity

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• Yajima, T., Nishimura, H., Sad, S., Shen, H., Kuwano, H., Yoshikai, Y. (2005). A Novel Role of IL-15 in Early Activation of Memory CD8+ CTL after Reinfection. J. Immunol. 174: 3590-3597 [Abstract] [Full Text]  
• Becker, T. C., Coley, S. M., Wherry, E. J., Ahmed, R. (2005). Bone Marrow Is a Preferred Site for Homeostatic Proliferation of Memory CD8 T Cells. J. Immunol. 174: 1269-1273 [Abstract] [Full Text]  

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