Myelin reactive T cells after T cell vaccination in multiple sclerosis: cytokine profile and depletion by additional immunizations

Pathogenic autoreactive T cells can be targeted by T cell vaccination (TCV) , a procedure in which patients are immunized with autologous attenuated pa thogenic T cells. We reported previously that TCV with myelin basic protein (MBP) reactive T cell clones in multiple sclerosis (MS) patients induced T cell immune responses, resulting in a clonal depletion of MBP reactive T c ells in all patients. Five years after TCV, MBP reactive T cells were obser ved in five out of nine MS patients. These clones had a different clonal or igin from those isolated before vaccination. We have studied the cytokine p rofile, cytotoxicity and epitope specificity of these reappearing clones. O ur data indicate that the clones express similar effector functions as thos e isolated before TCV, suggesting that they also could play a pathogenic ro le in the disease. We demonstrated that these clones can be depleted by an additional sequence of immunizations. These findings may be relevant to oth er T cell targeted immunotherapies for MS and other autoimmune diseases. (C ) 2000 Elsevier Science B.V. All rights reserved.