YTS-105

It is well established that long-term protection from insulin-dependent diabetes mellitus (IDDM) can be afforded to non-obese diabetic (NOD) mice by a short course of non-depleting (nd) anti-CD4 monoclonal antibodies (mAb). Since it is increasingly apparent that the CD8+ T cell plays a prominent role in the development of IDDM, we have investigated the effect of an anti-CD8 mAb (YTS 105) of the same isotype in both spontaneous and induced IDDM in NOD mice. Treatment with YTS 105 for 3 weeks was able to prevent the transfer of IDDM for a long period, and also substantially reduced spontaneous IDDM in female NOD mice. The role of the thymus in tolerance induction by these antibodies was studied. In the adult transfer model, thymectomized NOD mice, unlike their euthymic counterparts, were not protected long-term by treatment with YTS 105, and began to become overtly diabetic shortly after treatment. This was also true when the nd anti-CD4 mAb was used. Protection from spontaneous disease was not affected in the same way by thymectomy. The reasons for the observed effect of the thymus in the transfer model, and the differences between the two models that may explain the contrasting results are discussed.