Do anergic T cells induce suppressor T lymphocytes through idiotypic interactions?

Suppression by T cells and T cell anergy have been implied, at different periods of immunological research, as the main agents of peripheral down regulation of the immune response. This article discusses the possibility that anergic T cells, with the participation of appropriate co-stimulatory molecules on their membranes, stimulate CD8 cells with an alpha/beta TCR specific for peptides of the TCR of the anergic cell itself processed and presented by class I MHC. The non-anergic (orthoergic) members of the same clone, if activated, process and present their TCR in the same way, but, lacking the co-stimulatory molecule, are unable to stimulate the anti-idiotype CD8 cells. On the other hand the orthoergic, but not the anergic, cells can be induced into death (possibly by apoptosis) by the specific CD8 lymphocytes or, alternatively, can be pushed into the anergic pool by the same CD8 suppressors, thus contributing to the generation of a TCR-restricted circuit in which suppression is dominant. This simple immunosuppressive circuit can adequately explain some recent experiments on the course of experimental allergic encephalomyelitis. It is to be stressed that many elements of the proposal are hypothetical. They are, however, open to experimental study.