Expression of the IL-12 receptor beta 1 and beta 2 subunits in human tuberculosis.
To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response.
Zhang
M
M
Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler 75710, USA.
Gong
J
J
Presky
D H
DH
Xue
W
W
Barnes
P F
PF
D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*