Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 37 (6), 1678-90

IL-15-induced Human DC Efficiently Prime Melanoma-Specific Naive CD8+ T Cells to Differentiate Into CTL

Affiliations

IL-15-induced Human DC Efficiently Prime Melanoma-Specific Naive CD8+ T Cells to Differentiate Into CTL

Peter Dubsky et al. Eur J Immunol.

Abstract

Monocytes differentiate into dendritic cells (DC) in response to GM-CSF combined with other cytokines including IL-4 and IL-15. Here, we show that IL15-DC are efficient in priming naive CD8+ T cells to differentiate into melanoma antigen-specific cytotoxic T lymphocytes (CTL). While both melanoma peptide-pulsed IL15-DC and IL4-DC expand high-precursor frequency MART-1-specific CD8+ T cells after two stimulations in vitro, IL15-DC require much lower peptide concentration for priming. IL15-DC are more efficient in expanding gp100-specific CD8+ T cells and can expand CD8+ T cells specific for Tyrosinase and MAGE-3. CTL primed by IL15-DC are superior in their function as demonstrated by (i) higher IFN-gamma secretion, (ii) higher expression of Granzyme B and Perforin, and (iii) higher killing of allogeneic melanoma cell lines, most particularly the HLA-A*0201+ Sk-Mel-24 melanoma cells that are resistant to killing by CD8+ T cells primed with IL4-DC. Supernatants of the sonicated cells demonstrate unique expression of IL-1, IL-8 and IL-15. Therefore, membrane-bound IL-15 might contribute to enhanced priming by IL15-DC. Thus, IL-15 induces myeloid DC that are efficient in priming and maturation of melanoma antigen-specific CTL.

Similar articles

See all similar articles

Cited by 64 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback