Cutting edge: requirement for IL-15 in the generation of primary and memory antigen-specific CD8 T cells.
IL-15 and IL-15Ralpha are required for generation of memory-phenotype CD8 T cells in unimmunized mice. However, the role of IL-15 in primary expansion and generation of Ag-specific memory CD8 T cells in vivo has not been investigated. We characterized the CD8 T cell response against vesicular stomatitis virus (VSV) in IL-15(-/-) and IL-15Ralpha(-/-) mice. Surprisingly, IL-15 was required for primary expansion of VSV-specific CD8 T cells. The generation of VSV-specific memory CD8 T cells was also impaired without IL-15 signaling, and this defect correlated with a decrease in memory CD8 T cell turnover. Despite minimal proliferation without IL-15, a subset of memory cells survived long-term. IL-15Ralpha expression was low on naive CD8 T cells, up-regulated on Ag-specific effector cells, and sustained on memory cells. Thus, IL-15 was important for the generation and the subsequent maintenance of antiviral memory CD8 T cells.
Schluns
Kimberly S
KS
Division of Immunology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Williams
Kristina
K
Ma
Averil
A
Zheng
Xin X
XX
Lefrançois
Leo
L
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007156:Immunologic Memory / Q000235:genetics; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000502:physiology; D018353:Rhabdoviridae Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D018960:Hyaluronan Receptors; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2