Table I.
Potential mechanisms by which immunosuppressive drugs might promote the induction of allograft tolerance
| Mechanism | Agents |
|---|---|
| Attenuate rejection, thereby preventing destruction of allogeneic donor passenger leucocytes in the recipient lymphoid and nonlymphoid tissues | Not drug-specific |
| Allow B cell activation (in response to surviving donor cell surface antigens) which may contribute to network control of the immune systema | Not drug-specific |
| Increase thymic accrual of donor dendritic cells, allowing exposure of the immature host immune system to donor alloantigens | Tacrolimus, cyclosporin[50,51] |
| Allow movement of immature thymocytes to the periphery, resulting in further exposure of immature T cells to donor alloantigens | Tacrolimus, cyclosporin[52] |
| Permit replication and widespread dispersal of the donor passenger leucocyte population, with consequent continuous presentation of donor alloantigen to the recipient immune systema | Not drug-specific |
| Inhibit the second signal required for activation of host lymphocytes presented with foreign alloantigen, thus promoting an anergic response | Not drug-specific |
a
Although not drug-specific, these mechanisms would appear to be dependent on the avoidance of overimmunosuppression.