IFN-alpha2a 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.
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.
Padovan
Elisabetta
E
Research Division, Department of Surgery, University of Basel, Switzerland. epadovan@uhbs.ch
Spagnoli
Giulio C
GC
Ferrantini
Maria
M
Heberer
Michael
M
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000378:metabolism*; D011994:Recombinant Proteins
C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D017493:Leukocyte Common Antigens