Prevention of type 1 diabetes in the rat with an allele-specific anti-T-cell receptor antibody: Vβ13 as a therapeutic target and biomarker.

ABSTRACT: In earlier studies of the Iddm14 diabetes susceptibility locus in the rat, we identified an allele of the T-cell receptor (TCR) β-chain, Tcrb-V13S1A1, as a candidate gene. To establish its importance, we treated susceptible rats with a depleting anti-rat Vβ13 monoclonal antibody and then exposed them to either polyinosinic:polycytidylic acid or a diabetogenic virus to induce diabetes. The overall frequency of diabetes in the controls was 74% (n = 50), compared with 17% (n = 30) in the anti-Vβ13-treated animals, with minimal islet pathology in nondiabetic treated animals. T cells isolated from islets on day 5 after starting induction showed a greater proportion of Vβ13(+) T cells than did peripheral lymph node T cells. Vβ13 transcripts recovered from day 5 islets revealed focused Jβ usage a

SUBMITTER: Liu Z 

PROVIDER: S-EPMC3331757 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature