INTERVENTION WITH IMMUNOMODULATORY AGENTS - T-CELL VACCINATION

Current theories of the aetiology of RA point to a central role for the trimolecular complex comprising the MHC class II molecule on the surface of the APC, the antigenic peptide and the TCR on the disease-inducing T cell. Thus the arthritogenic T cell is an important target for new therapy. However, it cannot be directly identified because the causative antigen is unknown, so indirect techniques such as TCV and TCR peptide vaccination are required. In TCV, T cells thought to mediate the disease, in an activated andattenuated form, are injected into the patient, who then develops a specific immune response against these pathogenic T cells. TCV has been shown to be effective in protecting against and treating a variety of animal models of autoimmune disease, including AA, EAE and IDDM in NOD mice. The vaccines initially comprised clones and lines of T cells shown to be capable of transferring the disease, but later unseparated LN cells were also shown to be effective, paralleling more closely the human situation. Interestingly, it has become clear that TCV does not create its own regulatory network but amplifies a natural immunoregulatory network which forms as the disease develops. The major stimulating moiety on the vaccinating T cell is its receptor (anti-idiotypic response), although there is also an anti-ergotypic (anti-activated T cell) response. For this reason the technique of TCR peptide vaccination was developed, which utilizes only a short peptide from the TCR of the disease-causing cells to stimulate an immune response against them. This is effective in the prevention and treatment of EAE, where there is a preferential usage of TCR-Vβ8 by encephalitogenic T cells. The application of both these techniques to human autoimmune disease isin its infancy. Studies of TCV in MS and RA have not shown clear-cut clinical benefit, although immunological changes have been observed; comparison of methodology with the animal work and assessment of results are complex and further studies are in progress. Studies of TCR peptide vaccination in MS and RA are handicapped by the lack of a consensus on TCR usage in these conditions, but a limited study is underway in MS. © 1992 Baillière Tindall.