Type I IFN (IFN-αβ) is induced rapidly by infection and plays a key role in innate antiviral defense. IFN-αβ also exerts stimulatory effects on the adaptive immune system and has been shown to enhance Ab and T cell responses. We have investigated the importance of B and T cells as direct targets of IFN-αβ during IFN-α-mediated augmentation of the Ab response against a soluble protein Ag. Strikingly, the ability of IFN-α to stimulate the Ab response and induce isotype switching was markedly reduced in mice in which B cells were selectively deficient for the IFN-αβR. Moreover, IFN-α-mediated enhancement of the Ab response was also greatly impaired in mice in which T cells were selectively IFN-αβR-deficient. These results indicate that IFN-αβR signaling in both B and T cells plays an important role in the stimulation of Ab responses by IFN-αβ.

Type I IFN (IFN-αβ), which is produced rapidly in response to infection, plays a key role in innate immunity and also acts as a stimulus for the adaptive immune response. We have investigated how IFN-αβ induces cross-priming, comparing CD8+ T cell responses generated against soluble protein Ags in the presence or absence of IFN-αβ. Injection of IFN-α was found to prolong the proliferation and expansion of Ag-specific CD8+ T cells, which was associated with marked up-regulation of IL-2 and IL-15 receptors on Ag-specific cells and expression of IL-15 in the draining lymph node. Surprisingly, neither IL-2 nor IL-15 was required for IFN-α-induced cross-priming. Conversely, expression of the IFN-αβR by T cells was shown to be necessary for effective stimulation of the response by IFN-α. The finding that T cells represent direct targets of IFN-αβ-mediated stimulation reveals an additional mechanism by which the innate response to infection promotes adaptive immunity.

Summary Toll-like receptors (TLR) are believed to play a major role in the recognition of invading organisms, although their ability to shape immune responses is not completely understood. Our aim was to investigate in vivo the effect of different TLR stimuli on the generation of antibody responses and the induction of CD8 + T-cell crosspriming after immunization with soluble protein antigens. While all TLR agonists tested elicited the production of immunomodulatory cytokines, marked differences were observed in their ability to stimulate antigen-specific immune responses. Zymosan, poly(I:C) and CpG DNA, which signal through TLR2/6, 3 and 9, respectively, were found to strongly induce the production of IgG2a antibodies, whereas R-848 (TLR7) and LPS (TLR4) did so much more weakly. In contrast, LPS, poly(I:C) and CpG DNA, but not zymosan, induced functional CD8 + T-cell responses against OVA; peptidoglycan (TLR2/?) and R-848 were also ineffective in stimulating cross-priming. Experiments using IFN-α / β R-deficient mice showed that the induction of cross-priming by LPS and poly(I:C) was abrogated in the absence of IFN-α / β signalling, and induction by CpG DNA was greatly reduced. Overall, our results identify LPS as another TLR agonist that is able to generate functional cross-priming against a soluble protein antigen. In addition, our results demonstrate that the ability of TLR stimuli to initiate CD8 + T-cell responses against soluble protein antigens is largely dependent on the IFN-α / β signalling pathway.

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