T cell vaccination in secondary progressive multiple sclerosis

Four secondary progressive MS patients were vaccinated with bovine myelin-r eactive irradiated T cell lines from their peripheral blood. Patients were followed for 30-39 months, and monitored for Immunological responses toward the vaccine, and for their clinical characteristics. Two patients showed s table EDSS score over time, one patient showed improvement by one EDSS step , and in the remaining patient her EDSS advanced over time. After the secon d inoculation there was a progressive decline of circulating whole myelin-r eactive T cells. MBP143-168. PLP104-117. and MOG43-55-peptide-reactive T ce lls. In contrast the frequency of tetanus toroid-reactive T cells remained unchanged. T cell vaccination (TCV) was also associated with a decline of m yelin-specific IL-2- and IFN-gamma-secreting T cells. Twelve T cell lines ( TCL) that recognize the inoculates were isolated from the peripheral blood of two patients. Ten of these TCL were CD8(-) and lysed the inoculates in a MHC Class I restricted manner. The remaining two TCL were CD4(+), and lyse d the inoculates by MHC Class II restricted cytolytic activity. All T cell lines lysed not only myelin-reactive T cells, but also TCL specific for MBP 143-168. PLP104-117 and MOG43-55 peptides. Control TCL specific for tetanus toroid were not lysed. Neutralizing anti-Fas mAb did not influence the kil ling. Moreover, culture supernatants from two TCL which produce IL-10, were able to block the proliferation of myelin protein-specific TCL. This effec t was abrogated using mAbs specific for IL-10. The data obtained indicated that TCV using autologous irradiated bovine myelin-reactive T cells promote s an effective depletion of T cells reactive against different myelin antig ens. (C) 2000 Elsevier Science B.V. All rights reserved.