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Cell Stem Cell. 2013 May 2;12(5):546-58. doi: 10.1016/j.stem.2013.03.001. Epub 2013 Mar 21.

Expansion of functional human mucosal-associated invariant T cells via reprogramming to pluripotency and redifferentiation.

Author information

1
Department of Environmental Biology, School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. hwakao@med.hokudai.ac.jp

Abstract

Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor Vα7.2, CD161, and interleukin-18 receptor chain α. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.

PMID:
23523177
DOI:
10.1016/j.stem.2013.03.001
[Indexed for MEDLINE]
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