Document 0426
 DOCN  M9650426
 TI    IL-12, as an adjuvant, promotes a T helper 1 cell, but does not suppress
       a T helper 2 cell recall response.
 DT    9605
 AU    Bliss J; Van Cleave V; Murray K; Wiencis A; Ketchum M; Maylor R; Haire
       T; Resmini C; Abbas AK; Wolf SF; Genetics Institute Inc., Cambridge, MA
       02140, USA.
 SO    J Immunol. 1996 Feb 1;156(3):887-94. Unique Identifier : AIDSLINE
       MED/96144306
 AB    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.
 DE    Adjuvants, Immunologic/*PHARMACOLOGY  Animal  Antibody Specificity
       Female  Hemocyanin/IMMUNOLOGY  IgG/BIOSYNTHESIS  Immunologic
       Memory/*DRUG EFFECTS  Interleukin-12/*PHARMACOLOGY
       Interleukin-4/BIOSYNTHESIS  Lymph Nodes/IMMUNOLOGY  Mice  Mice, Inbred
       BALB C  Mice, Inbred C57BL  Mollusca  Spleen/IMMUNOLOGY  Th1 Cells/*DRUG
       EFFECTS/IMMUNOLOGY/METABOLISM  Th2 Cells/*DRUG
       EFFECTS/IMMUNOLOGY/METABOLISM  Trinitrobenzenes/IMMUNOLOGY  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).