Differential Activities of Immunogenic Collagen Type II Peptides in the Induction of Nasal Tolerance to Collagen-Induced Arthritis

Chu, Cong Qiu; Londei, Marco

doi:10.1006/jaut.1998.0255

Cited by 20 publications

(15 citation statements)

References 26 publications

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“…In the absence of CII Ab's, arthritis may progress, but generally has been found to be less severe (50,61,62). This is consistent with our previous results using APC-FasL gene therapy where lower levels of CII Ab's are observed (16).…”

Section: Figuresupporting

confidence: 90%

CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis

Liu¹,

Xu²,

Hsu³

et al. 2003

J. Clin. Invest.

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Previously, we described an APC-adenovirus (APC-Ad) FasL cell gene therapy method which could be used to deplete autoreactive T cells in vivo. FasL was toxic, however, and controlled regulation of FasL was not achieved. Here we describe an improved approach to delivering TNF-related apoptosis-inducing ligand (TRAIL) in vivo in which collagen II-induced (CII-induced) arthritis-susceptible (CIA-susceptible) DBA/1j mice were treated with CII-pulsed DCs that had been transfected with a novel Ad system. The Ad was engineered to exhibit inducible TRAIL under the control of the doxycycline-inducible (DOX-inducible) tetracycline response element (TRE). Four groups of mice were treated with CII-DCAdTRAIL+DOX, CII-DC-AdTRAIL (no DOX), CII-DC-AdGFP+DOX, or DC-AdTRAIL+DOX (no CII), beginning 2 weeks after priming with CII in CFA. The incidence of arthritis and infiltration of T cells in the joint was significantly decreased in CII-DC-AdTRAIL+DOX-treated mice. The in vitro splenic T cell proliferative response and induction of IFN-γ to bovine CII stimulation were also significantly reduced in mice treated with CII-DC-AdTRAIL+DOX. AdTRAIL+DOX was not toxic to DCs or mice but could induce activated T cells to undergo apoptosis in the spleen. Our results suggest that CII-DCAdTRAIL+DOX cell gene therapy is a safe and effective method for inhibiting the development of CIA.

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Section: Figuresupporting

confidence: 90%

CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis

Liu¹,

Xu²,

Hsu³

et al. 2003

J. Clin. Invest.

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“…Certainly different peptides of both CII in CIA and myelin in EAE vary in their ability to induce nasal tolerance (54)(55)(56). We know that peptides need to be immunogenic to induce tolerance (54).…”

Section: Discussionmentioning

confidence: 99%

Importance of dose of type II collagen in suppression of collagen-induced arthritis by nasal tolerance

Derry

Harper

Davies

et al. 2001

Arthritis & Rheumatism

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“…It has long been the goal to use these mechanisms to induce Ag-specific unresponsiveness in autoimmune diseases. Experimental approaches have included oral tolerance, nasal tolerance, and parenteral tolerance in a number of autoimmune disease models (11)(12)(13)(14)(15) as well as autoimmune diseases of man (14,16). However, the precise mechanism by which the Ag-specific T cell function is altered by exposure to the tolerogen is poorly understood.…”

mentioning

confidence: 99%

Detection of Early Changes in Autoimmune T Cell Phenotype and Function Following Intravenous Administration of Type II Collagen in a TCR-Transgenic Model

Brand

Myers

Whittington³

et al. 2002

The Journal of Immunology

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To study the phenotypic and functional changes in naive type II collagen (CII)-specific autoimmune T cells following a tolerogenic signal, a TCR-transgenic (Tg) mouse model of collagen-induced arthritis was developed. These Tg mice express an I-Aq-restricted CII (260–267)-specific TCR that confers severe accelerated autoimmune arthritis following immunization with CII. Despite the fact that >90% of the αβ T cells express the Tg, these mice can be rendered completely tolerant to the induction of arthritis by i.v. administration of 200 μg of CII. As early as 24 h after CII administration, CII-specific T cells demonstrated a decreased ability to proliferate in response to the CII immunodominant peptide and phenotypically altered the expression of L-selectin to CD62Llow and of phagocytic glycoprotein-1 to CD44high, expression levels consistent with the phenotype of memory T cells. In addition, they up-regulated the expression of the activation markers CD71 and CD69. Functionally, following tolerogenic stimulation, the CII-specific T cells produced similar levels of IL-2 in comparison to controls when challenged with CII peptide, however, by 48 h after exposure to tolerogen, IL-2 production dropped and was replaced by high levels of IL-10 and IL-4. Based on their production of Th2 cytokines, these data suggest that T regulatory cells expressing activation and memory markers are induced by the tolerogen and may exert their influence via cytokines to protect the animals from the induction of arthritis.

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Differential Activities of Immunogenic Collagen Type II Peptides in the Induction of Nasal Tolerance to Collagen-Induced Arthritis

Cited by 20 publications

References 26 publications

CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis

CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis

Importance of dose of type II collagen in suppression of collagen-induced arthritis by nasal tolerance

Detection of Early Changes in Autoimmune T Cell Phenotype and Function Following Intravenous Administration of Type II Collagen in a TCR-Transgenic Model

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