title: IL-12, as an adjuvant, promotes a T helper 1 cell, but does not suppress a T helper 2 cell recall response.
abstract: IL-12 is a potent inducer of NK and cytolytic T cell activity, IFN-gamma production, and T cell proliferation, and is necessary for differentiation of naive T cells to the Th1 subset. We have previously shown that IL-12 promotes a primary Th1 response and suppresses a primary Th2 response in lymph nodes of mice primed with a model hapten-protein conjugate, 2,4,6-trinitrophenyl (TNP)-keyhole limpet hemocyanin (KLH). We have now extended these studies to determine the Th phenotype of the recall response following immunization with soluble Ag and IL-12. For these experiments, mice were primed with TNP-KLH with or without treatment with IL-12, allowed to progress beyond the primary immune response, and challenged by i.p. injection of TNP-KLH. The phenotype of the recall response was monitored by measuring ex vivo production of IFN-gamma and IL-4 in Ag-stimulated lymph node and spleen cell cultures. Titer and isotype of TNP-specific serum Abs were also evaluated. Mice primed with Ag+IL-12 developed a Th1 recall response, as detected by KLH-specific IFN-gamma production from cultured spleen cells and the presence of TNP-specific IgG2a Ab in serum. However, they also developed an Ag-specific Th2 recall response, as characterized by Ag-induced IL-4 production from spleen cells and the presence of high titers of anti-TNP IgG1 in the serum. Studies of the cytokine profile during the primary response revealed that IL-12 induced in spleen cells the capacity to express both IL-4 and IFN-gamma. CD4+ T cells are necessary for production of IL-4 in the spleens of IL-12-treated mice, and most likely account for the Th2 recall response detected in mice primed with Ag+IL-12. These results indicate that the Th1 phenotype induced by immunization with IL-12 and Ag is maintained so that a Th1 recall response is expressed upon subsequent challenge with Ag. However, immunization with IL-12 also supports the development of a Th2 recall response, indicating that the Th1-inducing effect of IL-12 in vivo is not accompanied by a long lasting suppression of Th2 development.
authors.affiliation: Genetics Institute Inc., Cambridge, MA 02140, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bliss
authors.forename: V
authors.initials: V
authors.lastname: Van Cleave
authors.forename: K
authors.initials: K
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Wiencis
authors.forename: M
authors.initials: M
authors.lastname: Ketchum
authors.forename: R
authors.initials: R
authors.lastname: Maylor
authors.forename: T
authors.initials: T
authors.lastname: Haire
authors.forename: C
authors.initials: C
authors.lastname: Resmini
authors.forename: A K
authors.initials: AK
authors.lastname: Abbas
authors.forename: S F
authors.initials: SF
authors.lastname: Wolf
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D005260:Female; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000187:drug effects*; D018664:Interleukin-12 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008974:Mollusca; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D006241:Haptens; D007074:Immunoglobulin G; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; D018664:Interleukin-12; D015847:Interleukin-4; D006433:Hemocyanins