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Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase‐1 in rodents and in nonhuman primates
Author(s) -
Moreau A.,
Hill M.,
Thébault P.,
Deschamps J. Y.,
Chiffoleau E.,
Chauveau C.,
Moullier P.,
Anegon I.,
Alliot-Licht B.,
Cuturi M. C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-128173
Subject(s) - dendritic cell , in vitro , immune system , heme oxygenase , biology , immunology , in vivo , population , t cell , microbiology and biotechnology , bone marrow , chemistry , heme , medicine , enzyme , biochemistry , environmental health
Clinical translation of dendritic cell (DC)‐based cell therapy requires preclinical studies in nonhuman primates (NHPs). The aim of this work was to establish the in vitro conditions for generation of NHP tolerogenic DCs (Tol‐DCs), as well as to analyze the molecular mechanisms by which these cells could control an immune response. Two populations of NHP bone marrow‐derived DCs (BMDCs) were obtained: adherent and nonadherent. Although both populations displayed a quite similar phenotype, they were very different functionally. We characterized the adherent BMDCs as Tol‐DCs that were poor stimulators of T cells and actively inhibited T‐cell proliferation, whereas the nonadherent population displayed immunogenic properties in vitro. Interestingly, the anti‐inflammatory and immunosuppressive enzyme heme oxygenase‐1 (HO‐1) was up‐regulated in Tol‐DCs, compared to the immunogenic BMDCs. We demonstrated that HO‐1 mediates the immunosuppressive properties of Tol‐DCs in vitro (in NHPs and rats) and that HO‐1 is involved in the in vivo tolerogenic effect of Tol‐DCs in a rat model of allotransplantation. In conclusion, here we characterized the in vitro generation of NHP Tol‐DCs. Furthermore, we showed for the first time that HO‐1 plays a role in the active inhibition of T‐cell responses by rat and NHP Tol‐DCs.—Moreau, A., Hill, M., Thebault, P., Deschamps, J. Y., Chiffoleau, E., Chauveau, C., Moullier, P., Anegon, I., Alliot‐Licht, B., Cuturi M. C. Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase‐1 in rodents and in nonhuman primates. FASEB J. 23, 3070–3077 (2009). www.fasebj.org