期刊
JOURNAL OF IMMUNOLOGY
卷 177, 期 12, 页码 8410-8421出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.12.8410
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- NIAID NIH HHS [5P01 AI 051573, AI 10313] Funding Source: Medline
To determine whether strong CD4(+) T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogeneic form of survivin, a survival protein overexpressed in tumors, to maturing dendritic cells in lymphoid tissues. Dendritic cell targeting via the DEC205 receptor in the presence of anti-CD40 and poly(I:C) as maturation stimuli, induced strong human and mouse survivin-specific CD4(+) T cell responses, as determined by IFN-gamma, TNF-alpha, and IL-2 production, as well as the development of lytic MHC class II-restricted T cells and memory. Immunity was enhanced further by depletion of CD25(+)foxp3(+) cells before vaccination. anti-DEC205-human survivin was superior in inducing CD4(+) T cell responses relative to other approaches involving survivin plasmid DNA or survivin peptides with adjuvants. However, we were unable to induce CD8(+) T cell immunity to survivin by two doses of DEC205-targeted survivin or the other strategies. Therefore, significant CD4(+) T cell immunity to a self protein that is overexpressed in most human cancers can be induced by DEC205 targeting of the Ag in its xenogeneic form to maturing DCs.
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