Type I IFNs are immunomodulatory factors that possibly influence the properties of tissue-resident dendritic cells. Here, we have investigated the capacity of IFN-alpha2a to enhance DC chemoattractive and stimulatory capacity toward CD8+ T lymphocytes. Phenotypically, IFN-alpha2a-treated DC (IFN-DC) showed an increased expression of costimulatory and antigen-presenting molecules, maintained even after withdrawal of the cytokine. IFN-alpha2a enhanced DC stimulatory capacity toward CD8+ T cells, as assessed by increased MLR responses and induction of MART-1(26-35)-specific CTLs in vitro. No functional CCR7 chemokine receptor could be induced. Instead, high amounts of IP-10/CXCL10 and MIG/CXCL9 chemokines were produced. Freshly isolated CD8+RO+ cells and PHA-activated CD8+ T cells migrated efficiently in response to IFN-DC-conditioned medium, and the migration could be inhibited by neutralizing the CXCR3 receptor on responder cells. These results suggest that type I IFNs could enhance the elicitation of class I-restricted effector functions in vivo in the periphery by modulating DC chemoattractive properties.