Systemic administration of IL-15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells.
The systemic administration of IL-2 can act as a potent adjuvant for T cell-directed vaccine strategies. However, not only is the administration of IL-2 potentially toxic, but recent evidence suggests that it may also paradoxically limit the duration and magnitude of the cytotoxic T cell response. A recently identified cytokine, IL-15, shares many properties with IL-2 and may provide a preferential means of augmenting T cell-directed vaccine responses. Although well characterized in vitro, there are few data on the ability of IL-15 to augment T cell-mediated responses in vivo. We therefore evaluated the ability of systemic IL-15 to function as a T cell adjuvant in a murine vaccine model. To establish a population of easily identifiable Ag-responsive T cells, naive CD8(+) (OT-1) T cells were first adoptively transferred into mice. Vaccination with peptide-pulsed dendritic cells induced a modest expansion of OT-1 T cells. The addition of systemic IL-15 for 7 days following vaccination resulted in a significant increase in the expansion of responding T cells in the PBL, spleen, and lymph nodes. Importantly, the responding T cells were cytotoxic and maintained a Tc1-biased phenotype. We did not observe either enhanced resistance to activation-induced cell death or preferential generation of memory T cells as a result of treatment with IL-15 compared with IL-2. These studies show for the first time that IL-15 is capable of augmenting the primary CD8(+) T cell response to vaccination and contribute to the basis for future experiments exploring the clinical role of IL-15.
Rubinstein
Mark P
MP
Department of Surgery, Section of Surgical Oncology, Medical University of South Carolina, Charleston 29425, USA.
Kadima
Andre N
AN
Salem
Mohamed L
ML
Nguyen
Christophe L
CL
Gillanders
William E
WE
Cole
David J
DJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004527:Egg Proteins / Q000008:administration & dosage* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010446:Peptide Fragments; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; D019409:Interleukin-15; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin