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Analysis of infiltrating T cells in the affected autoimmune lesions of HTLV-I transgenic rats

, : Analysis of infiltrating T cells in the affected autoimmune lesions of HTLV-I transgenic rats. Hokkaido Journal of Medical Science 76(1): 35-47

Human T-cell leukemia virus type I(HTLV-I) is known to be associated with a number of disorders, inducing adult T cell leukemia, myelopathy, arthropathy, uveitis, and probably Sjögren's syndrome, T cell alveolitis, polymyositis, and infective dermatitis. To investigate the pathogenetic role of HTLV-I in these clinical disorders, we established a transgenic rat model carrying the env-pX gene of HTLV-I(env-pX rat), which develops arthritis, myocarditis, dermatitis, necrotizing arteritis, myositis and sialoadenitis. Several autoantibodies, such as anti-nuclear and anti-cardiolipin antibodies and rheumatoid factor, were detected in the sera. Peripheral T lymphocytes of env-pX rats expressed co-stimulatory molecules and showed hyper-immune reactivity to various stimulation in vitro. In this study, to characterize major pathogenic autoantigens in the affected lesions, the author examined the clonalities of T cells in the spleen and of infiltrating T cells in the skin lesions as well as affected joints of env-pX rats by single strand conformation polymorphism (SSCP) of polymerase chain reaction-amplified cDNA fragments of T cell receptor (TCR) V beta. No specific expansion of particular T cell clones was evident in the spleen of env-pX rats. Oligoclonal T cell expansions were observed in both infiltrating T cells of the affected joints and skin lesions, but no specific T cell clones common in the two lesions expanded in env-pX rats. Also, no specific amino acid motif in the complementarity determining region 3 of TCR V beta was evident in the affected joints. Those results suggest that the locally expanded T cell clones against various autoantigens of the joint or skin induced by the transgene may play major pathogenetic roles in development of autoimmune diseases in env-pX rats. On the other hand, env-pX rats easily developed arthritis by immunization of type II collagen and the SSCP patterns of accumulated T cell clonotypes in the arthritis were similar to those of arthritis developed in env-pX rats without immunization. The evidence suggests that the type II collagen-immunization may be a trigger to develop the inherent arthritis of env-pX rats.


PMID: 11235211

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