IL-12 secreting dendritic cells are required for optimum activation of human secondary lymphoid tissue T cells.
Successful immunization requires that mature dendritic cells (mDCs) prime T cells in secondary lymphoid tissue (LT). Previously, the authors have shown that LT T cell activation has an increased costimulatory threshold for a proliferative response as compared with peripheral blood (PB) T cells. Therefore, to optimize mDC immunogenicity, DC maturation was studied using LT T cells as responders. While mDCs obtained with soluble CD40Ligand (sCD40L) or a sCD40L/IFNgamma combination similarly expressed the CD83 and CCR7 molecules on their membrane, only the latter secreted IL-12. sCD40L/IFNgamma mDCs, as compared with sCD40L mDCs, enhanced allogeneic LT T cell proliferation, LT CD4+ cell IFNgamma production and LT CD8+ cell cytotoxicity. Enhancement could be predominantly ascribed to IL-12 secreted by sCD40L/IFNgamma mDCs and to additional costimulatory signals as shown remarkably in the IFNgamma response when IL-12 was neutralized. Therefore, in addition to their membrane phenotype, mDCs to be used in immunization protocols should be assessed for IL-12 secretion as a surrogate marker for an optimum costimulatory potential.
Rouard
Hélène
H
Department of Immunology, Henri-Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Etablissement Français du Sang, and University of Paris XII, Créteil, France.
Marquet
Jeanine
J
Léon
Anne
A
Maison
Patrick
P
Haioun
Corinne
C
Copie-Bergman
Christiane
C
Plonquet
Anne
A
Farcet
Jean-Pierre
JP
Delfau-Larue
Marie-Hélène
MH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice
D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma