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T cell activation by coxsackievirus B4 antigens in type 1 diabetes mellitus: evidence for selective TCR Vbeta usage without superantigenic activity.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2001 Sep 15; Vol. 167 (6), pp. 3513-20. - Publication Year :
- 2001
-
Abstract
- Numerous clinical and epidemiological studies link enteroviruses such as the Coxsackie virus group with the autoimmune disease type 1 diabetes mellitus (DM). In addition, there are reports that patients with type 1 DM are characterized by skewing of TCR Vbeta chain selection among peripheral blood and intraislet T lymphocytes. To examine these issues, we analyzed TCR Vbeta chain-specific up-regulation of the early T cell activation marker, CD69, on CD4 T cells after incubation with Coxsackievirus B4 (CVB4) Ags. CD4 T cells bearing the Vbeta chains 2, 7, and 8 were the most frequently activated by CVB4. Up-regulation of CD69 by different TCR families was significantly more frequent in new onset type 1 DM patients (p = 0.04), 100% of whom (n = 8) showed activation of CD4 T cells bearing Vbeta8, compared with 50% of control subjects (n = 8; p = 0.04). T cell proliferation after incubation with CVB4 Ags required live, nonfixed APCs, suggesting that the selective expansion of CD4 T cells with particular Vbeta chains resulted from conventional antigen processing and presentation rather than superantigen activity. Heteroduplex analysis of TCR Vbeta chain usage after CVB4 stimulation indicated a relatively polyclonal, rather than oligo- or monoclonal response to viral Ags. These results provide evidence that new-onset patients with type 1 DM and healthy controls are primed against CVB4, and that CD4 T cell responses to the virus have a selective TCR Vbeta chain usage which is driven by viral Ags rather than a superantigen.
- Subjects :
- Adult
Antigen Presentation
Antigen-Presenting Cells immunology
Antigens, CD biosynthesis
Antigens, CD genetics
Antigens, Differentiation, T-Lymphocyte biosynthesis
Antigens, Differentiation, T-Lymphocyte genetics
Autoimmune Diseases etiology
Cell Division
Coculture Techniques
Diabetes Mellitus, Type 1 etiology
Enterovirus B, Human pathogenicity
Enterovirus Infections complications
Enterovirus Infections virology
Female
Heteroduplex Analysis
Humans
Lectins, C-Type
Male
Superantigens immunology
Up-Regulation
Antigens, Viral immunology
Autoimmune Diseases immunology
CD4-Positive T-Lymphocytes immunology
Diabetes Mellitus, Type 1 immunology
Enterovirus B, Human immunology
Enterovirus Infections immunology
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
Lymphocyte Activation
Receptors, Antigen, T-Cell, alpha-beta genetics
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 167
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 11544345
- Full Text :
- https://doi.org/10.4049/jimmunol.167.6.3513