PT  - JOURNAL ARTICLE
AU  - Varela-Calvino, Ruben
AU  - Sgarbi, Gianluca
AU  - Wedderburn, Lucy R.
AU  - Dayan, Colin M.
AU  - Tremble, Jenny
AU  - Peakman, Mark
TI  - T Cell Activation by Coxsackievirus B4 Antigens in Type 1 Diabetes Mellitus: Evidence for Selective TCR Vβ Usage Without Superantigenic Activity
AID  - 10.4049/jimmunol.167.6.3513
DP  - 2001 Sep 15
TA  - The Journal of Immunology
PG  - 3513--3520
VI  - 167
IP  - 6
4099  - http://www.jimmunol.org/content/167/6/3513.short
4100  - http://www.jimmunol.org/content/167/6/3513.full
SO  - J. Immunol.2001 Sep 15; 167
AB  - 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 Vβ chain selection among peripheral blood and intraislet T lymphocytes. To examine these issues, we analyzed TCR Vβ 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 Vβ 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 Vβ8, 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 Vβ chains resulted from conventional antigen processing and presentation rather than superantigen activity. Heteroduplex analysis of TCR Vβ 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 Vβ chain usage which is driven by viral Ags rather than a superantigen.