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

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.

DEC205+ Dendritic Cell–Targeted Tolerogenic Vaccination Promotes Immune Tolerance in Experimental Autoimmune Arthritis

“…In BALB/c mice, immunization with human PG protein induces a form of arthritis (PGinduced arthritis [PGIA]) that recapitulates many clinical aspects of human RA (7,8). PGIA is a T cell-dependent and B cell-/Abmediated autoimmune disease (9)(10)(11)(12).…”

Chronic Follicular Bronchiolitis Requires Antigen-Specific Regulatory T Cell Control To Prevent Fatal Disease Progression

“…In addition to self-reactive T cells, a large number of B cells were recovered in the lungs of bigenic mice. Indeed, in an autoimmune TCR transgenic arthritis model, self-reactive T cells were shown to support autoantibody producing B cells (55). The large numbers of B cells accumulating in the lungs and forming peribronchiolar clusters suggests that B cells may also contribute to the observed pathology.…”