02536nas a2200469   4500000000100000008004100001260001600042653001800058653003100076653001600107653002000123653001100143653002100154653001900175653001900194653001800213653001200231653002600243653002800269653002500297653001900322653002500341653001400366100001600380700001300396700001500409700001700424700001300441700001500454700001300469700001300482700001500495700001100510700001400521700001200535700001500547245008400562300001200646490000800658520138600666022001402052       1994                            d  c1994 Oct 1510aBase Sequence10aCD8-Positive T-Lymphocytes10aDNA Primers10aGene Expression10aHumans10aInterferon-gamma10aInterleukin-1010aInterleukin-1210aInterleukin-410aleprosy10aLymphocyte Activation10aMolecular Sequence Data10aMycobacterium leprae10aRNA, Messenger10aT-Lymphocyte Subsets10aTh1 Cells1 aSieling P A1 aWang X H1 aGately M K1 aOliveros J L1 aMcHugh T1 aBarnes P F1 aWolf S F1 aGolkar L1 aYamamura M1 aYogi Y1 aUyemura K1 aRea T H1 aModlin R L00aIL-12 regulates T helper type 1 cytokine responses in human infectious disease.  a3639-470 v1533 a<p>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.</p>  a0022-1767