Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study
| Autor: | Heikki Hyöty, M. M. Zanone, Suzanne Bertera, William A. Rudert, Patrizia Luppi, Massimo Trucco, D. J. Becker, Catherine Haluszczak, Andrew L. Alexander |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent T-Lymphocytes Endocrinology Diabetes and Metabolism Lymphocyte Pilot Projects Antibodies Viral medicine.disease_cause Peripheral blood mononuclear cell Autoimmunity Islets of Langerhans Reference Values Risk Factors Internal medicine Diabetes mellitus Enterovirus Infections Internal Medicine medicine Humans Child biology Reverse Transcriptase Polymerase Chain Reaction Pancreatic islets T-cell receptor Middle Aged medicine.disease Immunoglobulin A Diabetes Mellitus Type 1 medicine.anatomical_structure Endocrinology Immunoglobulin M Child Preschool Immunoglobulin G Multigene Family Genes T-Cell Receptor beta Immunology biology.protein Female Antibody |
| Zdroj: | Diabetologia. 43:1484-1497 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s001250051559 |
| Popis: | Aims/hypothesis. High frequencies of T-cell receptor (TCR) Vβ7+ T cells were detected among the lymphocytes isolated from pancreatic islets of children at the onset of Type I (insulin-dependent) diabetes mellitus. We assessed whether a preferential expression of certain TCR Vβ gene families could also be detected among the peripheral blood mononuclear cells from diabetic patients. Methods. T-cell receptor repertoires were evaluated by using a semi-quantitative RT-PCR-based technique and confirmed by FACS analysis in peripheral blood mononuclear cells from diabetic patients before, at and after onset of the disease. These patients were also tested for exposure to enteroviruses by RT-PCR and by measuring titres of enterovirus-specific antibodies of the IgA, IgG, and IgM classes. Results. T-cell receptor Vβ7 gene family values were higher in recently-diagnosed diabetic patients (10.5 % ± 3.7) than in age-matched non-diabetic control subjects (5.1 % ± 1.6) (p < 0.001). In a time-course analysis of people who developed diabetes during clinical monitoring (i. e., converters), T-cell receptor Vβ7 gene expression showed values consistently above 10 % (p < 0.0005). Long-standing diabetic patients showed lower percentage of Vβ7 expression compared to values measured at disease onset. In the longitudinal study of the converters, multiple acute enterovirus infections were also detected. These infections appeared to be temporally related to increased percentage of Vβ7 gene transcripts. Conclusion/interpretation. The deviation in the T-cell receptor Vβ repertoire among circulating T cells from diabetic patients seems to re-emphasize the importance of enterovirus infections in accelerating the progression of Type I diabetes. [Diabetologia (2000) 43: 1484–1497] |
| Databáze: | OpenAIRE |
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