Differential expression of dendritic cell markers by all- trans retinoic acid on human acute promyelocytic leukemic cell line

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Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) for naive T cells and play an important role in cancer immunology. All- trans retinoic acid (ATRA) is known to be a differentiating agent in the treatment of acute promyelocytic leukemia (APL). In this study, we investigated whether ATRA can differentiate the retinoic acid (RA)-sensitive promyelocytic leukemic cell line, NB4, to DC-like cells and whether these differentiated cells can activate T cells. NB4 cells were differentiated to myeloid cells by 4, 6, and 8 days of ATRA treatment. NB4 cells up-regulated markers found in DCs, including HLA-DR, costimulatory molecules (CD80 and CD86), adhesion molecules (CD40), and chemokine receptors (CCR6) when cultured for 8 days in the presence of 1 μM ATRA. Upregulation of CD83 was also detected on the surface of ATRA-treated NB4 cells versus untreated cells. The addition of cytokines alone, such as GM-CSF or CD40 ligand, did not affect the expression of CD83 in untreated NB4 cells but they up-regulated CD83 in ATRA-treated cells. CD11b was coexpressed with CD80, CD83, and CD86 in ATRA-treated NB4 cells. In a functional assay, ATRA-treated NB4 cells stimulated T cell proliferation when challenged with Staphylococcus enterotoxin B. These results suggest that the differentiation of NB4 cells by ATRA causes the cells to express DC markers, and that ATRA-differentiated NB4 cells are able to present antigens to T cells.