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Interleukin-12: A bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency

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Abstract

Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine originally identified as a product of EBV-transformed B cell lines. Monocyte/macrophages are the physiologically most relevant producers of IL-12, in response to both Gram-positive and -negative bacteria, bacterial products, and intracellular parasites. Although IL-12 has an enhancing effect on the survival and growth of early hematopoietic progenitor cells, most of the IL-12 biological activity has been described on T and NK cells, on which it induces production of lymphokines, primarily IFN-γ, enhances cytotoxic activity, and, in cooperation with other stimuli, increases proliferation. IL-12 is an inducer of development of T helper type 1 (Th-1) cells and the equilibrium between IL-12 and IL-4 is probably important for the balancein vivo between Th-1 and Th-2 responses. IL-12 has an important role in the host resistance to infection, in particular to intracellular pathogens, by activating macrophages through induction of IFN-γ from NK and T cells and by enhancing cell-mediated immune responses, dependent on Th-1 cell development. Peripheral blood mononuclear cells from HIV-seropositive individuals are impaired in their ability to produce IL-12 in response to bacterial stimulation, and IL-12 restoresin vitro some of the depressed immunological functions, suggesting that a defect in IL-12 production may have a pathogenic role in the immunodeficiency of HIV-infected individuals. Natural IL-12 appears to provide a regulatory link between innate resistance and the development of the antigen-specific adaptive immune response and the recombinant protein has therapeutic potential because of its activity against tumors and infections and its effectiveness as an adjuvant enhancing cell-mediated immunity in vaccination.

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  1. Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, 3601 Spruce Street, 19104, Philadelphia, Pennsylvania

    Jihed Chehimi & Giorgio Trinchieri

  2. The Wistar Institute of Anatomy and Biology, 3601 Spruce Street, 19104, Philadelphia, Pennsylvania

    Jihed Chehimi & Giorgio Trinchieri

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Chehimi, J., Trinchieri, G. Interleukin-12: A bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency. J Clin Immunol 14, 149–161 (1994). https://doi.org/10.1007/BF01533364

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