IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T cells in rhesus macaques.
Using tetanus toxoid (TT) and influenza (Flu) immunization of rhesus macaques as a model, the effect of IL-2 and IL-15 on the generation and maintenance of antigen specific memory T cells was evaluated following primary and secondary immunization. Daily cytokine administration expanded primarily effector but not memory cells, while spacing cytokine administration to q3-7 days markedly enhanced TT and Flu specific memory responses. Following primary immunization, TT specific CD4 and influenza matrix protein (Flu-MP) specific CD8 effector responses were enhanced by IL-2 administration but CD8 specific memory responses were no different from cytokine non-treated monkeys. In contrast, expansion of Flu specific CD8 cells with IL-15 was only modest but resulted in significantly elevated levels of memory cells at 6 months. IL-15 also significantly enhanced early and late TT specific CD4 responses. The highest levels of primary effector and memory T cells were observed following alternate administration of both IL-2 and IL-15. Following booster immunization, however, only IL-15 appeared able to enhance CD8 T cell responses while IL-2 or IL2/IL-15 administration were less effective.
Department of Pathology and Laboratory Medicine, Emory University, Woodruff Memorial Building 2339, 1639 Pierce Drive, Atlanta, GA 30322, USA. fvillin@emory.edu
F
F
Villinger
R
R
Miller
K
K
Mori
A E
AE
Mayne
P
P
Bostik
J B
JB
Sundstrom
C
C
Sugimoto
A A
AA
Ansari
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D006207:Half-Life; D007114:Immunization; D007156:Immunologic Memory / Q000187:drug effects*; D007252:Influenza Vaccines / Q000276:immunology; D019409:Interleukin-15 / Q000493:pharmacokinetics / Q000494:pharmacology*; D007376:Interleukin-2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology
D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D019409:Interleukin-15; D007376:Interleukin-2; D013745:Tetanus Toxoid; D014613:Vaccines, Attenuated