Induction of IL-12 Secretion and Enhanced Surface Expression of B7.1/B7.2 and ICAM-1 in Human Monocytes Activated by the Vaccine Carrier Brucella Abortus: Correlation with in Vivo Generation of Cellular Immune Responses

  • H. Golding
  • M. B. Zaitseva
  • C. K. Lapham
  • B. Golding
Part of the NATO ASI Series book series (NSSA, volume 293)


It is well established that two cytokines, IFN-γ and IL-4, play an important role in the differentiation of Th0/Tc0 cells into effector types Th1/Tc1 or Th2/Tc2 cells during the initial phase of the immune response (O’Garra and Murphy, 1994). In addition to these lymphokines, it has been demonstrated that another cytokine, IL-12, is a pivotal positive factor in the differentiation of the Th1/Tc1 cell subset (Manetti et al, 1993). IL-12 is a heterodimeric protein consisting of p40 and p35 subunits (Kobayashi et al, 1989; Stern et al, 1990) that binds to its receptor of approximately 110 kDa (Chizzonite et al, 1992). The biologic activities of IL-12 include stimulatory effects on human NK cells and cytotoxic T cells (Bloom and Horvath, 1994; Chouaib et al, 1994; Kobayashi et al, 1989; Wolf et al, 1991), and induction of proliferation of activated, but not resting, CD4+ and CD8+ T cells (Bertagnolli et al, 1992; Gately at al, 1991; Perussia et al, 1992). IL-12 potentiates production of IFN-γ by Th1 and Th0 clones (Manetti et al, 1994), and also by NK and CD8+ cells (Croft et al, 1994; D’Andrea et al, 1992). Studies in the murine system demonstrated an important role for IL-12 in the development of immune protection against infectious agents such as Candida (Romani et al, 1992), Leishmania major (Afonso et al, 1994), Listeria in SCID mice (Tripp et al, 1994) and Schistosomiasis (Wynn et al, 1995). IL-12 was also shown to play an important role in IFN-γ-dependent protection against malaria (Sedegah et al, 1994) and tuberculosis (Zhang et al, 1994) in humans. The ability of IL-12 to induce protective immunity against many infections suggests that this cytokine should be a key component of vaccines designed to elicit strong cell-mediated immunity.


Human Immunodeficiency Virus Type Human Monocyte Human Natural Killer Cell Brucella Abortus P81S Cell 


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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • H. Golding
    • 1
  • M. B. Zaitseva
    • 1
  • C. K. Lapham
    • 1
  • B. Golding
    • 2
  1. 1.Laboratory of Retrovirus Research, Division of Viral Products, Center for Biologies Evaluation and ResearchUS Food and Drug AdministrationBethesdaUSA
  2. 2.Laboratory of Plasma Derivatives, Division of Hematology, Center for Biologies Evaluation and ResearchUS Food and Drug AdministrationBethesdaUSA

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