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(Journal of Leukocyte Biology. 2002;71:669-676.)
© 2002 by Society for Leukocyte Biology

IFN-2a induces IP-10/CXCL10 and MIG/CXCL9 production in monocyte-derived dendritic cells and enhances their capacity to attract and stimulate CD8⁺ effector T cells

Elisabetta Padovan^*, Giulio C. Spagnoli^*, Maria Ferrantini and Michael Heberer^*

^* Research Division, Department of Surgery, University of Basel, Switzerland; and
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy

Correspondence: Elisabetta Padovan, Research Division, Department of Surgery, University of Basel, Hebelstr. 20, Basel, Switzerland. E-mail: epadovan{at}uhbs.ch

Type I IFNs are immunomodulatory factors that possibly influence the properties of tissue-resident dendritic cells. Here, we have investigated the capacity of IFN-2a to enhance DC chemoattractive and stimulatory capacity toward CD8⁺ T lymphocytes. Phenotypically, IFN-2a-treated DC (IFN-DC) showed an increased expression of costimulatory and antigen-presenting molecules, maintained even after withdrawal of the cytokine. IFN-2a 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.

Key Words: type I IFNs • chemokines • CTL • tumor immunity

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