title: STAT4 is required for the generation of Th1 and Th2, but not Th17 immune responses during monophosphoryl lipid A adjuvant activity.
abstract: STAT4 is critical for the production of IFN-γ during the generation of Th1 immune responses. We investigated the role of STAT4 in mediating Th1-inducing activity of a vaccine adjuvant monophosphoryl lipid A (MPL-A) using the standard antigen ovalbumin (OVA) in STAT4KO mice. Our results show that splenocytes from STAT4KO mice displayed lower OVA-specific T-cell proliferation and IL-2 production compared with wild-type (WT) mice. Further, IFN-γ production was diminished in STAT4KO-derived splenocytes but the levels of IL-12 and TNF-α were similar compared with WT mice. Interestingly, STAT4 deficiency also led to a decrease in IL-10 and Th2 cytokines such as IL-4 and IL-13 upon MPL-A immunization, although IL-17 production was similar between WT- and STAT4KO-derived splenocytes. Our observations for defective Th1 and Th2 responses in STAT4KO mice were further supported by the low levels of Th1-associated IgG2a and Th2-associated IgG1 in the sera of these mice. Taken together, our results show that STAT4 plays a critical role in mediating both Th1 and Th2 responses upon immunization with MPL-A. Our study provides a better understanding of how MPL-A mediates T-cell activation which will be critical for future vaccine development.
authors: Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors: Sanjay
authors: S
authors: Varikuti
authors: Department of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH 43210, USA.
authors: Steve
authors: S
authors: Oghumu
authors: Department of Microbiology, Ohio State University, Columbus, OH 43210, USA.
authors: Gayathri
authors: G
authors: Natarajan
authors: Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors: Jennifer
authors: J
authors: Kimble
authors: Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors: Rachel H
authors: RH
authors: Sperling
authors: Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA.
authors: Ellen
authors: E
authors: Moretti
authors: Department of Pediatrics, Indiana University, Indianapolis, IN 46202, USA.
authors: Mark H
authors: MH
authors: Kaplan
authors: Department of Pathology, Ohio State University Medical Center, 1645 Neil Avenue, Columbus, OH 43210, USA abhay.satoskar@osumc.edu.|Department of Microbiology, Ohio State University, Columbus, OH 43210, USA.
authors: Abhay R
authors: AR
authors: Satoskar
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D050797:STAT4 Transcription Factor / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D008050:Lipid A; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; C048436:monophosphoryl lipid A
keywords: IFN-γ; IL-2; IL-4; T cells; vaccine