Format

Send to

Choose Destination
Int Immunol. 2012 Aug;24(8):507-17. doi: 10.1093/intimm/dxs057. Epub 2012 Apr 19.

Arthritogenic T cells drive the recovery of autoantibody-producing B cell homeostasis and the adoptive transfer of arthritis in SCID mice.

Author information

1
Department of Molecular Medicine, Rush University Medical Center, Chicago, IL 60612, USA. kkistoth@bidmc.harvard.edu

Abstract

T cells orchestrate joint inflammation in rheumatoid arthritis (RA), but B cells/B cell-derived factors are also involved in disease pathogenesis. The goal of this study was to understand the role of antigen-specific T and B cells in the pathological events of arthritis, which is impossible to study in humans due to the small number of antigen-specific cells. To determine the significance of antigen-specific lymphocytes and antibodies in the development of an autoimmune mouse model of RA, we generated TCR transgenic (TCR-Tg) mice specific for the dominant arthritogenic epitope of cartilage proteoglycan (PG) and performed a series of combined transfers of T cells, B cells and autoantibodies into BALB/c.Scid mice. The adoptive transfer of highly purified T cells from naive TCR-Tg, arthritic TCR-Tg or arthritic wild-type mice induced arthritis in SCID recipients, but the onset and severity of the disease were dependent on the sequential events of the T cell-supported reconstitution of PG-specific B cells and autoantibodies. The presence of activated PG-specific T cells was critical for disease induction, establishing a unique milieu for the selective homeostasis of autoantibody-producing B cells. In this permissive environment, anti-PG autoantibodies bound to cartilage and induced activation of the complement cascade, leading to irreversible cartilage destruction in affected joints. These findings may lead to a better understanding of the complex molecular and cellular mechanisms of RA.

PMID:
22518822
PMCID:
PMC3406935
DOI:
10.1093/intimm/dxs057
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center