RESUMO
Optimal strategies for antigen-specific melanoma vaccination are currently being defined in experimental mouse models. Using a single H2-K(b)-binding peptide epitope derived from the melanosomal enzyme tyrosinase-related protein 2 (TRP2) in C57BL/6 mice, we show that adenovirus-transduced dendritic cells (DC) are clearly superior to peptide-pulsed DC for the induction of CD8+ T cells and antimelanoma immunity. Vaccine efficacy strictly depended on the presence of linked CD4+ T-cell help during the priming but not the effector phase of the immune response. These results provide important information for the translation of melanoma vaccine strategy in future clinical applications.
Assuntos
Adenoviridae/genética , Vacinas Anticâncer/uso terapêutico , Células Dendríticas/imunologia , Oxirredutases Intramoleculares/uso terapêutico , Melanoma Experimental/prevenção & controle , Fragmentos de Peptídeos/imunologia , Vacinação , Animais , Antígenos CD4/genética , Antígenos CD4/fisiologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , DNA Recombinante/farmacologia , Proteínas de Fluorescência Verde/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fragmentos de Peptídeos/síntese química , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Linfócitos T Citotóxicos/imunologia , Transdução GenéticaRESUMO
Hyperhomocysteinemia is a risk factor for ischemic stroke. We investigated five functional polymorphisms involved in homocysteine metabolism in each 159 stroke patients and controls. The folate-sensitive polymorphism methylenetetrahydrofolate reductase (MTHFR) c. 677 C > T (A222V) referred a non-significant risk of ischemic stroke (odds ratio: 1.20) in all patients, and homozygosity for MTHFR c. 677 C > T was associated with an earlier onset of stroke selectively in patients younger than 60 years (38 +/- 3 years vs. 45 +/- 1 years; P = 0.043). This study suggests that the investigated polymorphisms are no major risk factors for stroke, although MTHFR c. 677 C > T could be a minor factor of vulnerability especially in young patients (TT genotype), which might be helpful for the clinical work-up of stroke cases and for preventive dietary strategies.
