IL-12-independent Th1 polarization in human mononuclear cells infected with varicella-zoster virus.
T helper type 1 (Th1) cells perform a critical role in fighting intracellular organisms, and interleukin-12 (IL-12) is known to promote a Thl response. This study was conducted to identify whether an IL-12-independent Th1 reaction is induced by the varicella-zoster virus (VZV) in human beings. It was found that different intracellular microorganisms could induce IFNgamma but not IL-12 production. Induction of IFNgamma production by VZV was associated with IFNalpha production and phosphorylation of both the signal transducer and activator of transcription-1 (STAT-1) and STAT-4 in lymphocytes. In contrast, Bacillus Calmette-Guerin (BCG) induced IL-12 production in association with STAT-4 but not STAT-1 activation. Anti-IFNalpha but not anti-IL-12 antibodies blocked the VZV-induced Th1 polarization. A patient with an IL-12 receptor beta1 chain deficiency showed a normal VZV- but not a normal BCG-induced Th1 reaction, further supporting the concept of an IFNalpha-mediated, IL-12-independent Th1 reaction in response to certain intracellular infections. Identification of the early Th1 polarization induced by IFNalpha versus IL-12 in response to specific viruses may enable the development of better therapeutic strategies tailored to different infections.
Yu
Hong-Ren
HR
Department of Pediatric Allergy, Immunology and Rheumatology, Chang Gung Children's Hospital, Kaohsiung, Taiwan.
Chen
Rong-Fu
RF
Hong
Kuo-Ching
KC
Bong
Chin-Nam
CN
Lee
Wen-I
WI
Kuo
Ho-Chang
HC
Yang
Kuender D
KD
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*
C508438:IL12RB1 protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma