Both Langerhans cells and interstitial DC cross-present melanoma antigens and efficiently activate antigen-specific CTL.
Dendritic cells (DC) have a unique capacity to present external antigens to CD8(+) T cells, i.e. cross-presentation. However, it is not fully established whether the ability to cross-presentation is restricted to a unique subset of DC in humans. Here, we show that two major myeloid DC subsets, i.e. Langerhans cells (LC) and interstitial DC (Int-DC), have the ability to cross-present antigens to CD8(+) T cells in vitro. LC and Int-DC were obtained from DC generated by culturing human CD34(+)-hematopoietic progenitor cells with GM-CSF, FLT3-L, and TNF-alpha (CD34-DC). Both DC subsets were able to capture necrotic/apoptotic allogeneic melanoma cells and present antigens to CD8(+) T cells, resulting in efficient priming of naive CD8(+) T cells into CTL capable of killing melanoma cells. Strikingly, a single stimulation with either subset (LC or Int-DC) or total CD34-DC loaded with necrotic/apoptotic melanoma cells was sufficient to activate melanoma-specific memory CD8(+) T cells obtained from patients with metastatic melanoma to become effective CTL. Thus, this study provides the rationale to use CD34-DC loaded with necrotic/apoptotic allogeneic melanoma cells in a clinical trial.
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Tinghua
T
Cao
Hideki
H
Ueno
Casey
C
Glaser
Joseph W
JW
Fay
A Karolina
AK
Palucka
Jacques
J
Banchereau
D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology*; D017209:Apoptosis; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018952:Antigens, CD34; D000951:Antigens, Neoplasm