Direct stimulation of T cells by type IIFN enhances the CD8+ T cell response during cross-priming

Type I IFN (IFN-alpha beta), 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-alpha beta,6 induces cross-priming, comparing CD8(+) T cell responses generated against soluble protein Ags in the presence or absence of IFN-alpha beta. Injection of IFN-alpha 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-alpha-induced cross-priming. Conversely, expression of the IFN-alpha beta R by T cells was shown to be necessary for effective stimulation of the response by IFN-alpha. The finding that T cells represent direct targets of IFN-alpha beta-mediated stimulation reveals an additional mechanism by which the innate response to infection promotes adaptive immunity.