A PROTEOGLYCAN (AGGRECAN)-SPECIFIC T-CELL HYBRIDOMA INDUCES ARTHRITIS IN BALB/C MICE

Aggrecan, the high buoyant density cartilage proteoglycan (PG), has been shown to induce progressive polyarthritis and ankylosing spondylitis in genetically susceptible BALB/c mice. To further characterize the nature of the autopathogenic effector T cells operating in these mice and to determine the region(s) of the PG molecule recognized by these T cells, we generated PC-specific T cell hybridomas from arthritic mice. One of the PC-specific T cell hybridomas (5/4E8), when injected into naive irradiated BALB/c mice, was capable of inducing clinical and histopathologic signs of arthritis. Massive swelling and redness of the paws dominated the clinical picture. A reactive synovial cell proliferation, the accumulation of hybridoma and inflammatory cells in the enlarged joint space, the loss of PC from the superficial layer of the articular cartilage, and the erosion of articular surface were identical histopathologic signs to those found either in primary or adoptive transfer of PC-induced arthritis. The PC-specific and arthritogenic T cell hybridoma (5/4E8) expressed TCR-alpha beta(+) (V beta 4), CD4(+), and CD8(-) phenotypes and belonged to the Th1 subset, as the cells secreted IL-2 and IFN-gamma, but not IL-4 upon PC stimulation, and the response was MHC class II (I-A(d))-restricted. These observations provide direct evidence that PC-specific Th cells play crucial roles in autoimmune arthritic processes.