Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression.
To characterize the mechanism by which interleukin 10 (IL-10) inhibits Th1 responses to intracellular pathogens, we evaluated the interaction between IL-10 and Mycobacterium tuberculosis-induced gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells from persons across the spectrum of tuberculous infection. M. tuberculosis-induced IFN-gamma production was highest in healthy tuberculin reactors, intermediate in human immunodeficiency virus (HIV)-negative tuberculosis patients, and lowest in HIV-infected tuberculosis patients. Neutralizing antibodies to IL-10 increased IFN-gamma production in HIV-infected and HIV-negative tuberculosis patients by enhancing monocyte IL-12 production. Expression of the T-cell-costimulatory molecule CTLA-4 was depressed in M. tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients, and anti-IL-10 and Il-12 upregulated expression of CTLA-4. These findings provide evidence that intracellular pathogens can inhibit Th1 responses and downregulate expression of specific costimulatory molecules.
Gong
J H
JH
Department of Medicine, University of Southern California School of Medicine, Los Angeles, 90033, USA.
Zhang
M
M
Modlin
R L
RL
Linsley
P S
PS
Iyer
D
D
Lin
Y
Y
Barnes
P F
PF
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis*; D018106:CD28 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D018796:Immunoconjugates; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D016753:Interleukin-10; D018664:Interleukin-12; D000069594:Abatacept; D007371:Interferon-gamma