@article{17872, keywords = {Base Sequence, CD8-Positive T-Lymphocytes, DNA Primers, Gene Expression, Humans, Interferon-gamma, Interleukin-10, Interleukin-12, Interleukin-4, leprosy, Lymphocyte Activation, Molecular Sequence Data, Mycobacterium leprae, RNA, Messenger, T-Lymphocyte Subsets, Th1 Cells}, author = {Sieling P A and Wang X H and Gately M K and Oliveros J L and McHugh T and Barnes P F and Wolf S F and Golkar L and Yamamura M and Yogi Y and Uyemura K and Rea T H and Modlin R L}, title = {IL-12 regulates T helper type 1 cytokine responses in human infectious disease.}, abstract = {

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.

}, year = {1994}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {153}, pages = {3639-47}, month = {1994 Oct 15}, issn = {0022-1767}, language = {eng}, }