RESUMO
A T-cell receptor (TCR) peptide vaccine from the V beta 5.2 sequence expressed in multiple sclerosis (MS) plaques and on myelin basic protein (MBP)-specific T cells boosted peptide-reactive T cells in patients with progressive MS. Vaccine responders had a reduced MBP response and remained clinically stable without side effects during one year of therapy, whereas nonresponders had an increased MBP response and progressed clinically. Peptide-specific T helper 2 cells directly inhibited MBP-specific T helper 1 cells in vitro through the release of interleukin-10, implicating a bystander suppression mechanism that holds promise for treatment of MS and other autoimmune diseases.
Assuntos
Doenças Autoimunes/terapia , Imunoterapia Ativa , Esclerose Múltipla/terapia , Fragmentos de Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Vacinas/imunologia , Adulto , Doenças Autoimunes/imunologia , Progressão da Doença , Método Duplo-Cego , Feminino , Antígenos HLA-DR/análise , Cadeias HLA-DRB1 , Humanos , Interleucina-10/fisiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Projetos Piloto , Subpopulações de Linfócitos T/imunologia , Células Th2/imunologia , Vacinas/administração & dosagemRESUMO
Immunization with disease-associated TCR V region peptides is an effective treatment for experimental autoimmune encephalomyelitis. Myelin basic protein-specific T cells, which induce experimental autoimmune encephalomyelitis in many animal strains, may be important in the pathogenesis of multiple sclerosis. Myelin basic protein-specific T cell clones from some multiple sclerosis patients preferentially use TCR V genes from the V beta 5.2 and V beta 6.1 families. To assess the safety and immunogenicity of TCR V beta 5.2 and V beta 6.1 peptides, we injected 11 multiple sclerosis patients with varying doses of two synthetic peptides, TCR V beta 5.2(39-59) and V beta 6.1(39-59), encompassing the CDR2 region of these V gene families. Low doses (100 to 300 micrograms) of peptide induced T cell immunity in 7 of 11 patients to one or both peptides. Delayed type hypersensitivity skin responses to the peptides were observed in three of seven responders, and TCR peptide-specific Ab occurred in two of seven T cell responders. Low doses of TCR peptides produced no side effects and did not cause broad spectrum immunosuppression. Synthetic TCR V region peptides can induce T cell immunity safely in humans and may prove useful in treating human autoimmune diseases.