IL-12 regulates T helper type 1 cytokine responses in human infectious disease.
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.
Sieling
P A
PA
Division of Dermatology, University of California-Los Angeles, School of Medicine 90024.
Wang
X H
XH
Gately
M K
MK
Oliveros
J L
JL
McHugh
T
T
Barnes
P F
PF
Wolf
S F
SF
Golkar
L
L
Yamamura
M
M
Yogi
Y
Y
Uyemura
K
K
Rea
T H
TH
Modlin
R L
RL
D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000494:pharmacology; D007918:Leprosy / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma