A MINIMAL MODEL FOR T-CELL VACCINATION

We have developed a mathematical model for the regulation of the growt h of autoreactive T cells (the T cells responsible for autoimmunity). The model is very simple in that it is based only on the fundamental p roperties of T cells. However, despite this simplicity, it can account for a variety of phenomena referred to as T-cell vaccination. The pur pose of T-cell vaccination is to create resistance to autoimmunity. Th is can be achieved by injecting either a subpathogenic quantity of aut oreactive T cells, or attenuated autoreactive cells, or cells that rec ognize the autoreactive cells. The results of our model are based on t he assumption that the self antigens involved in T-cell vaccination ar e normally not expressed; thus the autoreactive T lymphocytes are neit her activated nor negatively selected. Self tolerance, therefore, corr esponds to a 'passive' state. T-cell vaccination induces a transition From this passive state of tolerance to an active state of tolerance. In this state the autoreactive cells are controlled by regulator cells which recognize the autoreactive cells. The model predicts a qualitat ive difference between vaccination with normal autoreactive cells and vaccination with attenuated autoreactive cells, Normal cells may give rise to a permanent switch to the vaccinated state; attenuated cells, however, can provide only transient protection, which is dose dependen t. Preliminary experimental data confirm this prediction. Finally, we propose a speculative explanation for relapsing autoimmune disease.