Dissociated induction of cytotoxicity and DTH by CFA and CpG

Abstract

Vaccinations typically rely on immunization with live virus for eliciting protective CD8 T cell immunity. There is increasing interest to use subunit vaccination strategies to achieve such responses. Complete Freund's adjuvant (CFA) and unmethylated cytosine-guanine dinucleotide containing DNA are considered some of the most potent adjuvants for eliciting immunity. Whereas a wealth of information is available on how these adjuvants affect CD4 T cell responses, their effects on engaging CD8 T cell immunity are not completely understood. We immunized C57BL/6J mice with the class I restricted peptides Uty or SIINFEKL using these 2 adjuvants and tested for cytokine secretion, proliferation, in vivo cytotoxicity, and delayed-type hypersensitivity (DTH). Our data show that CFA-induced CD8 T cells to proliferate, mediate DTH, and to secrete interferon-gamma, interleukin (IL)-2 and IL-17. Despite these markers of CD8 T cell activation, CFA failed to induce an early cytotoxic CD8 T cell response. In contrast, unmethylated cytosine-guanine dinucleotide containing DNA promoted a vigorous cytolytic response without activating substantial cytokine production, proliferation or DTH. These data have implications for CD8 T cell subunit vaccine design in which cytotoxicity versus DTH plays a key role in host defense.