Please use this identifier to cite or link to this item: https://repository.monashhealth.org/monashhealthjspui/handle/1/32552
Title: An IL-12-independent role for CD40-CD154 in mediating effector responses: Studies in cell-mediated glomerulonephritis and dermal delayed-type hypersensitivity.
Authors: Timoshanko J.R.;Ruth A.-J.;Li M.;Semple T.J.;Tipping P.G.;Kitching A.R. ;Holdsworth S.R. 
Institution: (Ruth, Kitching, Li, Semple, Timoshanko, Tipping, Holdsworth) Department of Medicine, Monash University, Monash Medical Centre, Clayton, Vic., Australia (Holdsworth) Department of Medicine, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton, Vic. 3168, Australia
Issue Date: 18-Oct-2012
Copyright year: 2004
Publisher: American Association of Immunologists (9650 Rockville Pike, Bethesda MD 20814, United States)
Place of publication: United States
Publication information: Journal of Immunology. 173 (1) (pp 136-144), 2004. Date of Publication: 01 Jul 2004.
Abstract: Crescentic glomerulonephritis (GN) results from IL-12-driven Th1-directed cell-mediated responses (akin to delayed-type hypersensitivity (DTH)) directed against glomerular Ags. CD40-CD154 interactions are critical for IL-12 production and Th1 polarization of immune responses. Crescentic anti-glomerular basement membrane GN was induced in C57BL/6 (wild-type (WT)) mice (sensitized to sheep globulin) by planting this Ag (as sheep anti-mouse glomerular basement membrane globulin) in their glomeruli. Crescentic GN did not develop in CD40-/- mice due to significantly reduced nephritogenic Th1 responses. IL-12 was administered to CD40-/- mice with GN to dissect interactions between IL-12 and CD40 in inducing nephritogenic immunity and injury. Administration of IL-12 to CD40-/- mice restored Th cell IFN-gamma production, and up-regulated intrarenal chemokines and glomerular T cell and macrophage accumulation compared with WT control mice. Despite this, renal macrophages were not activated and renal injury and dermal DTH were not restored. Thus, CD40-directed IL-12 drives Th1 generation and effector cell recruitment but CD40 is required for activation. To test this hypothesis, activated OT-II OVA-specific CD4+ cells and OVA323-339- loaded nonresponsive APCs were transferred into footpads of WT, CD40 -/-, and macrophage-depleted WT mice. WT mice developed significant DTH compared with CD40-/- and macrophage-depleted WT mice. This study demonstrated that CD40-induced IL-12 is required for generation of systemic Th1 immunity to nephritogenic Ags, and that IL-12 enhances Th1 effector cell recruitment to peripheral sites of Ag presentation via generation of local chemokines. Effector cell activation, renal DTH-like injury, and dermal DTH require direct Th1 CD154/macrophage CD40 interactions.
DOI: http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.4049/jimmunol.173.1.136
PubMed URL: 15210767 [http://www.ncbi.nlm.nih.gov/pubmed/?term=15210767]
ISSN: 0022-1767
URI: https://repository.monashhealth.org/monashhealthjspui/handle/1/32552
Type: Article
Subjects: male
mouse
nonhuman
priority journal
sensitization
*skin allergy/et [Etiology]
adolescent
Th1 cell
immune injury/et [Etiology]
macrophage
macrophage activation
antigen presenting cell
article
*cellular immunity
controlled study
cytokine production
*delayed hypersensitivity/et [Etiology]
effector cell
*glomerulonephritis/et [Etiology]
kidney injury/et [Etiology]
globulin
*CD40 antigen/ec [Endogenous Compound]
*CD40 ligand/ec [Endogenous Compound]
chemokine
gamma interferon/ec [Endogenous Compound]
*interleukin 12
nephritogenic antigen
crescentic glomerulonephritis/et [Etiology]
animal cell
animal model
animal tissue
antigen presentation
*skin allergy / *etiology
adolescent
animal cell
animal model
animal tissue
antigen presentation
antigen presenting cell
article
*cellular immunity
controlled study
cytokine production
*delayed hypersensitivity / *etiology
effector cell
*glomerulonephritis / *etiology
immune injury / etiology
kidney injury / etiology
macrophage
macrophage activation
male
mouse
nonhuman
priority journal
sensitization
Th1 cell
Appears in Collections:Articles

Show full item record

Page view(s)

8
checked on Aug 17, 2024

Google ScholarTM

Check


Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.