Efficient Production of Functional Human NKT Cells from Induced Pluripotent Stem Cells − Reprogramming of Human Vα24+iNKT Cells

Sep 20, 2021Bio-protocol

Efficient Creation of Working Human NKT Immune Cells from Reprogrammed Stem Cells

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Abstract

Antigen-specific T cell-derived induced pluripotent stem cells (iPSCs) may serve as a source for functional T cells useful in cancer immunotherapy.

Vα24iNKT cells are a subset of T cells that recognize specific glycolipids presented by CD1d.
These cells can produce IFN-γ, which is associated with enhancing anti-tumor responses.
The study outlines a protocol to reprogram human Vα24iNKT cells into iPSCs and subsequently re-differentiate them back into functional Vα24iNKT cells.
Methods to measure the activity of re-differentiated Vα24iNKT cells are also provided.

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Antigen-specific T cell-derived induced pluripotent stem cells (iPSCs) have been shown to re-differentiate into functional T cells and thus provide a potential source of T cells that could be useful for cancer immunotherapy. Human Vα24invariant natural killer T (Vα24iNKT) cells are subset of T cells that are characterized by the expression of an invariant Vα24-Jα18 paired with Vβ11, that recognize glycolipids, such as α-galactosylceramide (α-GalCer), presented by the MHC class I-like molecule CD1d. Vα24iNKT cells capable of producing IFN-γ are reported to augment anti-tumor responses, which affects both NK cells and CD8cytotoxic T lymphocytes to eliminate MHC- and MHCtumor cells, respectively. Here we describe a robust protocol to reprogram human Vα24iNKT cells into iPSC, and then to re-differentiate them into Vα24iNKT cells (iPS-Vα24iNKT). We further provide a protocol to measure the activity of iPS-Vα24iNKT cells. + + + + + + + + +

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