Systemic administration of IL-15 augments the antigen-specific primary CD8+ T cell response following vaccination with peptide-pulsed dendritic cells

Mark P. Rubinstein, Andre N. Kadima, Mohamed L. Salem, Christophe L. Nguyen, William E. Gillanders, David J. Cole

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4928-4935
Number of pages8
JournalJournal of Immunology
Volume169
Issue number9
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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