title: Differential outcome of IL-2/anti-IL-2 complex therapy on effector and memory CD8+ T cells following vaccination with an adenoviral vector encoding EBV epitopes.
abstract: IL-2/anti-IL-2 complex-based therapy has been proposed as a potential adjunct therapeutic tool to enhance in vivo efficacy of T cell-based immunotherapeutic strategies for chronic viral infections and human cancers. In this study, we demonstrate that IL-2 complex therapy can have discerning effects on CD8(+) T cells depending on their stage of differentiation. To delineate the underlying mechanism for these opposing effects on CD8(+) T cells, we examined the effects of IL-2 therapy during early priming, effector, and memory phases of T cell responses generated following immunization with an adenoviral vector encoding multiple EBV CD8(+) epitopes. IL-2 complex treatment during the early priming phase, which coincided with low levels of IL-2Rβ (CD122) and higher levels of IL-2Rα (CD25) on CD8(+) T cells, did not induce the expansion of effector T cells. In contrast, IL-2 complex treatment following the establishment of memory enhanced the expansion of Ag-specific T cells. Additionally, central memory T cells preferentially expanded following treatment at the expense of effector memory T cell populations. These studies demonstrate how differentiation status of the responding CD8(+) T cells impacts on their responsiveness to IL-2 complexes and highlight that timing of treatment should be considered before implementing this therapy in a clinical setting.
authors.affiliation: Tumour Immunology Laboratory, Australian Centre for Vaccine Development, Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinez
authors.forename: Jesse
authors.initials: J
authors.lastname: Peet
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000276:immunology*; D007156:Immunologic Memory; D007371:Interferon-gamma; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D053646:Interleukin-2 Receptor beta Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000939:Epitopes; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma