Homeostatic proliferation but not the generation of virus specific memory CD8 T cells is impaired in the absence of IL-15 or IL-15Ralpha.
The generation and efficient maintenance of antigen specific memory T cells is essential for long-lasting immunological protection. Antigen specific memory CD8 T cells are known to be maintained via antigen-independent homeostatic proliferation. However, signals that drive memory T cell generation and/or influence the slow turnover of memory T cells are unknown. Recently, IL-15 has received attention for its potential effect on memory CD8 T cells. In this report we examine the role of 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 a chain. Both cytokine and receptor deficient mice mount a robust CD8 T cell response to infection with lymphocytic choriomeningitis virus (LCMV) that is initially only slightly lower than in control mice. Further, virus specific memory CD8 T cells are generated in both IL-15 -/- and IL-15Ralpha -/- mice. However, longitudinal analysis reveals a slow attrition of LCMV specific memory CD8 T cells in the absence of IL-15 signals. Indeed, direct examination of homeostatic proliferation reveals a severe defect in the turnover of antigen specific memory CD8 T cells in the absence of IL-15. Together these results suggest 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.
Wherry
E John
EJ
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Becker
Todd C
TC
Boone
David
D
Kaja
Murali-Krishna
MK
Ma
Averil
A
Ahmed
Rafi
R
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D021122:Protein Subunits; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2