TY - JOUR KW - Base Sequence KW - CD8-Positive T-Lymphocytes KW - DNA Primers KW - Gene Expression KW - Humans KW - Interferon-gamma KW - Interleukin-10 KW - Interleukin-12 KW - Interleukin-4 KW - leprosy KW - Lymphocyte Activation KW - Molecular Sequence Data KW - Mycobacterium leprae KW - RNA, Messenger KW - T-Lymphocyte Subsets KW - Th1 Cells AU - Sieling P A AU - Wang X H AU - Gately M K AU - Oliveros J L AU - McHugh T AU - Barnes P F AU - Wolf S F AU - Golkar L AU - Yamamura M AU - Yogi Y AU - Uyemura K AU - Rea T H AU - Modlin R L AB -

We investigated the role of IL-12 in regulating T cell and cytokine responses in human infectious disease by using the spectrum of leprosy as a model. Tuberculoid patients mount strong T cell responses to Mycobacterium leprae, with production of the type 1 cytokines IL-2 and IFN-gamma in lesions; whereas lepromatous patients manifest weak T cell responses to M. leprae, with production of the type 2 cytokines IL-4 and IL-10 in lesions. We found expression of IL-12 p40 mRNA, as measured by PCR amplification, and IL-12 p70, as measured by immunohistochemistry, to be 10-fold greater in tuberculoid lesions than in lepromatous lesions. The ability of M. leprae to stimulate release of IL-12 from monocytes was inhibited by rIL-4 and rIL-10. M. leprae-induced T cell proliferation in tuberculoid patients was blocked by the addition of neutralizing Abs to IL-12. Furthermore, rIL-12 stimulated proliferation of CD4+ type 1 T cell clones from tuberculoid lesions, but not CD8+ type 2 T cell clones from lepromatous lesions; however, both responded to rIL-2, rIL-12 augmented M. leprae-specific T cell proliferation in lepromatous patients, thereby causing the selective expansion of CD4+ T cells and increasing T cell IFN-gamma production. These data indicate that IL-12 is an important mediator in the generation of the type 1 cytokine response in human infectious disease.

BT - Journal of immunology (Baltimore, Md. : 1950) C1 - http://www.ncbi.nlm.nih.gov/pubmed/7930584?dopt=Abstract DA - 1994 Oct 15 IS - 8 J2 - J. Immunol. LA - eng N2 -

We investigated the role of IL-12 in regulating T cell and cytokine responses in human infectious disease by using the spectrum of leprosy as a model. Tuberculoid patients mount strong T cell responses to Mycobacterium leprae, with production of the type 1 cytokines IL-2 and IFN-gamma in lesions; whereas lepromatous patients manifest weak T cell responses to M. leprae, with production of the type 2 cytokines IL-4 and IL-10 in lesions. We found expression of IL-12 p40 mRNA, as measured by PCR amplification, and IL-12 p70, as measured by immunohistochemistry, to be 10-fold greater in tuberculoid lesions than in lepromatous lesions. The ability of M. leprae to stimulate release of IL-12 from monocytes was inhibited by rIL-4 and rIL-10. M. leprae-induced T cell proliferation in tuberculoid patients was blocked by the addition of neutralizing Abs to IL-12. Furthermore, rIL-12 stimulated proliferation of CD4+ type 1 T cell clones from tuberculoid lesions, but not CD8+ type 2 T cell clones from lepromatous lesions; however, both responded to rIL-2, rIL-12 augmented M. leprae-specific T cell proliferation in lepromatous patients, thereby causing the selective expansion of CD4+ T cells and increasing T cell IFN-gamma production. These data indicate that IL-12 is an important mediator in the generation of the type 1 cytokine response in human infectious disease.

PY - 1994 SP - 3639 EP - 47 T2 - Journal of immunology (Baltimore, Md. : 1950) TI - IL-12 regulates T helper type 1 cytokine responses in human infectious disease. VL - 153 SN - 0022-1767 ER -