T cell vaccination in secondary progressive multiple sclerosis.
Four secondary progressive MS patients were vaccinated with bovine myelin-reactive 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 stable EDSS score over time, one patient showed improvement by one EDSS step, and in the remaining patient her EDSS advanced over time. After the second inoculation there was a progressive decline of circulating whole myelin-reactive T cells, MBP143-168, PLP104-117, and MOG43-55-peptide-reactive T cells. In contrast the frequency of tetanus toxoid-reactive T cells remained unchanged. T cell vaccination (TCV) was also associated with a decline of myelin-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 lysed 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 MBP143-168, PLP104-117 and MOG43-55 peptides. Control TCL specific for tetanus toxoid were not lysed. Neutralizing anti-Fas mAb did not influence the killing. Moreover, culture supernatants from two TCL which produce IL-10, were able to block the proliferation of myelin protein-specific TCL. This effect was abrogated using mAbs specific for IL-10. The data obtained indicated that TCV using autologous irradiated bovine myelin-reactive T cells promotes an effective depletion of T cells reactive against different myelin antigens.
Correale
J
J
Department of Neurology, USC School of Medicine, 1333 San Pablo Street, MCK 142, Los Angeles, CA 90033, USA. jcorreale@fleni.org.ar
Lund
B
B
McMillan
M
M
Ko
D Y
DY
McCarthy
K
K
Weiner
L P
LP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000917:Antibody Formation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D002417:Cattle; D002460:Cell Line; D004185:Disability Evaluation; D053222:Fas Ligand Protein; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology* / Q000628:therapy*; D009185:Myelin Proteins / Q000276:immunology*; D010865:Pilot Projects; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination / Q000379:methods*
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009185:Myelin Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma