Triggering a second T cell receptor on diabetogenic T cells can prevent induction of diabetes

In this paper, we test the hypothesis that triggering of a second T cell re ceptor (TCR) expressed on diabetogenic T cells might initiate the onset of diabetes. A cross between two TCR-transgenic strains, the BDC2.5 strain tha t carries diabetogenic TCRs and the A18 strain that carries receptors speci fic for C5, was set up to monitor development of diabetes after activation through the C5 TCR. F1 BDC2.5 X A18 mice developed diabetes spontaneously b eyond 3-4 mo of age. Although their T cells express both TCRs constitutivel y, the A18 receptor is expressed at extremely low levels. In vitro activati on of dual TCR T cells followed by adoptive transfer into neonatal or adult Fl mice resulted in diabetes onset and death within 10 d after transfer. I n contrast, in vivo immunization of F1 mice with different forms of C5 anti gen not only failed to induce diabetes but protected mice from the spontane ous onset of diabetes. We propose that antigenic stimulation of cells with low levels of TCR produces signals inadequate for full activation, resultin g instead in anergy.