RESUMO
OBJECTIVE: Human T cell leukemia virus type I env-pX transgenic rats (env-pX rats) were used to investigate the pathogenesis of arthritis. METHODS: Phenotype of cells infiltrated into arthritic joints in env-pX rats was analyzed using flow cytometry and cell-transfer experiments were done using env-pX and wild-type WKAH rats. RESULTS: The majority of T cells infiltrated into arthritic joints in env-pX rats exhibited a CD4 and activated phenotype. Transfer of these T cells into articular space in wild-type WKAH rats succeeded to induce arthritis similarly seen in env-pX rats. However, injection of the cells into sites other than joints did not induce inflammation. Transfer of in vitro-stimulated lymph node cells from disease-free env-pX rats into articular space did not induce arthritis in wild-type WKAH rats. CONCLUSION: These findings suggest that articular tissues carrying the env-pX transgene are required for generation of arthritogenic T cells in env-pX rats. However, the constitutive antigens other than the transgene products are recognized as immunological targets by the arthritogenic T cells in the advanced arthritic joints. Molecules expressed specifically in articular tissues may be needed to maintain the inflammatory cell infiltration.
Assuntos
Artrite Experimental/patologia , Produtos do Gene env/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Articulações/patologia , Proteínas Oncogênicas de Retroviridae/genética , Linfócitos T/patologia , Fatores de Transcrição/genética , Transferência Adotiva , Animais , Animais Geneticamente Modificados , Artrite Experimental/genética , Artrite Experimental/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Produtos do Gene env/metabolismo , Infecções por HTLV-I , Humanos , Articulações/metabolismo , Ratos , Ratos Endogâmicos , Proteínas Oncogênicas de Retroviridae/metabolismo , Linfócitos T/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Virais Reguladoras e AcessóriasRESUMO
We have earlier reported that diverse collagen vascular diseases, including arthritis, arteritis, thrombosis, myocarditis, myositis, sialo-/dacryoadenitis and dermatitis develop with the advent of autoantibodies in transgenic rats carrying the LTR-env-pX gene of human T lymphocyte virus type I (LTR-env-pX rats). To clarify the pathogenesis of these collagen vascular diseases, immunological features of LTR-env-pX rats were examined. In LTR-env-pX rats affected with these diseases, expression of CD80/86 on both tissue-infiltrating and peripheral T cells increased, compared with findings in non-transgenic rats with experimental inflammatory diseases. CD80/86 was also upregulated on peripheral T cells in LTR-env-pX rats prior to the development of diseases. Lymphocytes from LTR-env-pX rats showed an increase in autologous proliferation and were hyperreactive against several mitogens, including concanavalin A, immobilized anti-CD3 antibodies, and superantigens in vitro. Antigen-specific immune response was also enhanced in LTR-env-pX rats. The collective evidence indicates that lymphocytes of LTR-env-pX rats constitutively express surface molecules related to T cell activation and are immunologically hyperresponsive. Bone marrow cell transfer from LTR-env-pX rats to lethally irradiated non-transgenic rats revealed that these immunologically pre-activated and hyperresponsive lymphocytes play a critical role in the pathogenesis of several collagen vascular diseases, especially of dermatitis in LTR-env-pX rats.
Assuntos
Doenças do Colágeno/imunologia , Genes env , Genes pX , Vírus Linfotrópico T Tipo 1 Humano/genética , Vasculite/imunologia , Animais , Animais Geneticamente Modificados , Antígenos CD/análise , Antígeno B7-1/análise , Antígeno B7-2 , Contagem de Células , Modelos Animais de Doenças , Infecções por HTLV-I/imunologia , Molécula 1 de Adesão Intercelular/análise , Glicoproteínas de Membrana/análise , Miocardite/imunologia , Ratos , Linfócitos T/imunologiaAssuntos
Animais Geneticamente Modificados/genética , Doenças Autoimunes/genética , Especificidade de Órgãos/imunologia , Ratos Endogâmicos/genética , Proteínas Oncogênicas de Retroviridae/genética , Fatores de Transcrição , Animais , Autoimunidade , Expressão Gênica , Técnicas de Transferência de Genes , Linfócitos/imunologia , Masculino , Ratos , Proteínas Virais Reguladoras e AcessóriasRESUMO
Various genetic factors and environmental factors are intricately intertwined in the pathomechanism of autoimmune diseases. Retroviruses, represented by HTLV-I and HIV, are known to relate to autoimmune disorders. However, the pathogenetic role of retrovirus and the relationship between retrovirus and autoimmune diseases are not clear. We found autoimmune diseases, such as arthritis, myositis, arteritis, dermatitis and T cell abnormality in HTLV-I transgenic rats, and studied the pathomechanism of the diseases by cell transfer experiments. Here we describe the relationship between retrovirus and autoimmune diseases and suggest that retrovirus plays a important role in the autoimmune diseases.