Superantigens in insulin-dependent diabetes mellitus

Luppi, Patrizia; Trucco, Massimo

doi:10.1007/bf01795133

Cited by 11 publications

(8 citation statements)

References 199 publications

(217 reference statements)

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“…The study of the TCR-Vb gene segment expression required individual amplification of at least 26 TCR-Vb families and subfamilies [40,41] using a panel of 5'-Vb primers together with a 6-carboxyfluorescein (6-FAM, Applied Biosystems, Foster City, Calif., USA) 3'-Cb oligonucleotide. The Vb and Cb oligonucleotide primers were used at a final concentration of 0.5 mmol/l each in the 50 ml final reaction mixture.…”

Section: Methodsmentioning

confidence: 99%

“…The Vb and Cb oligonucleotide primers were used at a final concentration of 0.5 mmol/l each in the 50 ml final reaction mixture. As an internal positive control for each Vb family segment, a pair of constant region oligonucleotides 5'-Ca and 3'-Ca, also tagged with 4,7,2',7'-Tetrachloro-6-carboxyfluorescein, (6-TET; Applied Biosystems), were used at a final concentration of 0.2 mmol/l [40,41]. Twenty-eight cycles of PCR were carried out to remain in the exponentially increasing part of the reaction [42].…”

Section: Methodsmentioning

confidence: 99%

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Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

et al. 2000

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Type I (insulin-dependent) diabetes mellitus is an autoimmune disease characterized by infiltrating lymphocytes in the Langerhans' islets and by destruction of insulin-producing beta cells [1]. Despite many years of intensive studies, the precise cause and mechanisms triggering the beta-cell-specific attack still remain undetermined. The less than 50 % concordance for the disease between monozygotic twins suggests, however, that a complex interplay occurs between genetic and non-genetic factors (i. e., environmental) [2,3]. In particular, epidemiological evidence supports a role for infectious agents in the development and/or progression of Type I diabetes [4±10].Although the possibility of a virus-mediated etiopathogenesis of Type I diabetes still remains a central point of discussion, certain viral infections, especially Diabetologia (2000) Abstract Aims/hypothesis. High frequencies of T-cell receptor (TCR) Vb7 + 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 Vb 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 Vb7 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 timecourse analysis of people who developed diabetes during clinical monitoring (i. e., converters), T-cell receptor Vb7 gene expression showed values consistently above 10 % (p < 0.0005). Long-standing diabetic patients showed lower percentage of Vb7 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 Vb7 gene transcripts. Conclusion/interpretation. The deviation in the T-cell receptor Vb 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] Keywords Type I diabetes, etiology, autoimmunity, Coxsackievirus, T cell receptor.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Restricted TCR Vβ gene expression and enterovirus infection in Type I diabetes: a pilot study

et al. 2000

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“…27 For each tissue specimen, the analysis was performed at least 3 times from RT-PCR to gel reading. Genescan also allows the analysis of the different lengths of the CDR3, inclusive of V␤, (N) D␤ (N), and J␤ segments, the corresponding peaks, and their areas (spectratypes).…”

Section: Selected Abbreviations and Acronymsmentioning

confidence: 99%

Idiopathic Dilated Cardiomyopathy

et al. 1998

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Background-Many cases of idiopathic dilated cardiomyopathy (IDC) result from an inflammatory myocarditis. The specific immunological mechanisms are not yet defined. Various autoimmune diseases are associated with superantigentriggered immune responses, resulting in massive T-cell activation and tissue damage. We studied 3 cases in a search for evidence that such a phenomenon is also implicated in IDC. Methods and Results-Myocardial, lymph node, and thymic tissue samples were obtained from IDC patients who were undergoing heart transplantation. Infiltrating immune-cell phenotypes and gene expression of T-cell receptor (TCR) ␣-and ␤-chain variable (V␣ and V␤) regions were analyzed by immunostaining and polymerase chain reaction. Similar technical approaches were used to assay the tissues for the presence of coxsackievirus B (CVB). In all the specimens analyzed, an overexpression of the TCR V␤3, V␤7, and V␤13.1 gene families was detected among the infiltrating T cells. These tissues were also found to be CVB3-positive. In vitro exposure of peripheral blood mononuclear cells to lysates of cells infected with CVB3 was capable of stimulating expansion of the same TCR V␤ families. The TCR V␣ repertoire was never found to be skewed. Conclusions-A superantigen-mediated immune response is involved in human heart disease. CVB3 may directly or indirectly trigger this response, suggesting a possible mechanistic link between CVB infection and myocarditis development progressing to IDC. (Circulation. 1998;98:777-785.)

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“…The study of the TCR V gene segment usage requires individual amplification of at least 26 TCR V families and subfamilies, as previously described [17,18]. Two microlitres of the PCR mixtures containing the V gene family amplified cDNA were resolved by electrophoresis on an ABI 377 DNA Sequencer and automatically analysed by GENESCAN 2.1 software (Applied Biosystems Inc.) [18].…”

Section: Evaluation Of Tcr V Repertoiresmentioning

confidence: 99%