Characterization of T Cell Phenotype and Function in a Double Transgenic (collagen-specific TCR/HLA-DR1) Humanized Model of Arthritis

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2014 Jan 11

PMID 24405551

Citations 10

Authors

Bo Tang

Seunghyun Kim

Sarah Hammond

David L Cullins

David D Brand

Edward F Rosloniec

John M Stuart

Arnold E Postlethwaite

Andrew H Kang

Linda K Myers

Affiliations

Soon will be listed here.

Abstract

Introduction: T cells orchestrate joint inflammation in rheumatoid arthritis (RA), yet they are difficult to study due to the small numbers of antigen-specific cells. The goal of this study was to characterize a new humanized model of autoimmune arthritis and to describe the phenotypic and functional changes that occur in autoimmune T cells following the induction of pathological events.

Methods: We developed a double transgenic mouse containing both the HLA-DR1 transgene and an HLA-DR1-restricted collagen-specific TCR in order to obtain large numbers of antigen-specific T cells that can be used for immunologic studies.

Results: In vitro, CII-specific T cells from this mouse proliferated vigorously in response to the CII immunodominant peptide A2 and the cells altered their phenotype to become predominately CD62Llow and CD44high "activated" T cells. The response was accompanied by the production of Th1, Th2, and Th17-type cytokines. Following immunization with bovine CII/CFA, these mice develop an accelerated arthritis compared to single transgenic HLA-DR1 mice. On the other hand, when the mice were treated orally with the analog peptide A12, (a suppressive analog of collagen we have previously described), arthritis was significantly suppressed, despite the fact that >90% of the CD4+ T cells express the TCR Tg. In GALT tissues taken from the A12-treated mice, IL-2, IFN-γ, and IL-17 production to the autoimmune collagen determinant dropped while high levels of IL-10 and IL-4 were produced.

Conclusions: We have developed a humanized model of autoimmune arthritis that will be useful for the study of T cell directed therapies as well as T cell mediated mechanisms of autoimmune diseases.

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Leukocyte-associated immunoglobulin-like receptor 1 inhibits T-cell signaling by decreasing protein phosphorylation in the T-cell signaling pathway.

Park J, Brand D, Rosloniec E, Yi A, Stuart J, Kang A J Biol Chem. 2020; 295(8):2239-2247.

PMID: 31932281 PMC: 7039569. DOI: 10.1074/jbc.RA119.011150.

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