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In Vitro Differentiation of Adult Bone Marrow Progenitors into Antigen-Specific CD4 Helper T Cells Using Engineered Stromal Cells Expressing a Notch Ligand and a Major Histocompatibility Complex Class II Protein
Author(s) -
Bingbing Dai,
Pin Wang
Publication year - 2009
Publication title -
stem cells and development
Language(s) - English
Resource type - Journals
eISSN - 1557-8534
pISSN - 1547-3287
DOI - 10.1089/scd.2008.0021
Subject(s) - biology , stromal cell , major histocompatibility complex , microbiology and biotechnology , bone marrow , progenitor cell , immunology , in vitro , antigen , stem cell , cancer research , genetics
A murine stromal cell line (OP9-DL1) expressing a notch ligand, Delta-like-1, has been shown to be able to drive the differentiation of both murine and human hematopoietic progenitors into T cells in vitro. Further studies showed that hematopoietic progenitors transduced by a retroviral vector to express a human CD8 T-cell receptor (TCR) followed by an OP9-DL1 monolayer coculture could generate antigen-specific cytotoxic T lymphocytes in vitro. It remains unknown if a similar method could be applied to produce CD4 helper T cells. In this report, we show that murine adult bone marrow (BM) cells transduced with an OT2 CD4 TCR and cocultured with OP9 stromal cells expressing Delta-like-1 can differentiate into antigen-specific CD4 T cells in vitro. These cells are capable of inducing the expression of T-cell activation markers and producing cytokines upon stimulation. We have also constructed a new stromal cell line (OP9-DL1-IA(b)) ectopically expressing a murine major histocompatibility complex class II protein, I-A(b), in OP9-DL1 cells. This new line could accelerate the development of TCR-transduced BM cells into CD4 T cells, resulting in cells with an improved capacity to respond to T-cell stimulation to secrete cytokines. Taken together, we demonstrate a general and potentially useful method to generate autologous antigen-specific CD4 helper T cells in vitro from easily accessible BM cells.

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