Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent.

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Research Abstract Details 

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Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Abstract Text:

Mythily Srinivasan,Rajaraman Eri,Susan L Zunt,Don-John Summerlin,David D Brand,Janice S Blum,

OBJECTIVE: The CD80/CD86-CD28/CD152 costimulatory pathways transmit signals for CD4+ T cell activation and suppression and are critically involved in the pathogenesis of rheumatoid arthritis (RA). A significant number of CD4+ T cells and macrophages in the rheumatoid synovium express elevated levels of CD80, increasing the potential for costimulation in trans of naive T cells. To determine the effect of blockade of this costimulatory axis in RA, we designed novel CD80-binding peptides and evaluated their therapeutic potential in collagen-induced arthritis (CIA), an animal model of RA. METHODS: The conserved MYPPPY motif of CD152 adopts a polyproline type II (PPII) helical conformation in the CD80-CD152 complex. The pairing preferences of the critical residues at the CD80-CD152 interface and their propensity to form PPII helices were integrated to design peptides with optimum PPII helical content that selectively block CD80-receptor interactions. The clinical efficacy was tested in DBA/1LacJ mice that were administered the CD80 blocking agents, called CD80-binding competitive antagonist peptides (CD80-CAPs), at the time of immunization with bovine type II collagen or 3 weeks after immunization. RESULTS: A single administration of select CD80-CAPs significantly reduced the clinical, radiologic, and histologic disease severity in CIA. Importantly, administration of CD80-CAPs during activated immune response significantly suppressed disease development by reducing mononuclear cell infiltration in the joints and mediating peripheral deletion of activated CD4+ T cells. CONCLUSION: A rationally designed CD80-binding peptide both prevents and suppresses CIA, suggesting a potential application in RA. Apoptosis of activated CD4+ T cells following in vivo blockade suggests that the effects of CD80-CAPs may be long-lasting.

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Publishing Authors By Initials

M Srinivasan,R Eri,SL Zunt,DJ Summerlin,DD Brand,JS Blum,

For similar musculoskeletal system: skeleton: joints: joint capsule: synovial membrane research abstracts see: musculoskeletal system: skeleton: joints: joint capsule: synovial membrane research

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Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Arthritis and rheumatism

VOLUME: 56

Page Numbers: 498-508

Journal Abbreviation: Arthritis Rheum.

ISSN: 0004-3591

DAY: 3

MONTH: Feb

YEAR: 2007

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370605

Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Keywords Mesh Terms:

KEYWORDS: Synovial Membrane

MESH TERMS: metabolism

Chemical & Substance for Abstract: Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent. Information

Substance Name: Collagen

Registry Number: 9007-34-5

Grant and Affiliation Information for Suppression of immune responses in collagen-induced arthritis by a rationally designed CD80-binding peptide agent.

AFFILIATION: Indiana University, Indianapolis, and Indiana University-Purdue University, IN 46202, USA. mysriniv@iupui.edu

Country: United States

AGENCY: United States NIAMS

GRANT: R03-AR-051411-01

ACRONYM: AR

MEDLINETA: Arthritis Rheum

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