Expansion of Functional Human Mucosal-Associated Invariant T Cells via Reprogramming to Pluripotency and Redifferentiation
| Autor: | Hiroshi Wakao, Kazunori Yoshikiyo, Kei Enomoto, Hiroyoshi Fujita, Hisanori Minakami, Manami Ohtaka, Tomoko Furukawa, Mahito Nakanishi, Yusuke Yasutomi, Nobuyuki Harada, Rika Wakao, Olivier Lantz, Jyunji Tanaka, Ken Nishimura, Uichi Koshimizu, Kazue Higuchi, Tomoyuki Sasaki, Atsushi Oda, Tomofumi Tanaka, Takashi Yamada, Yukie Sekiya, Tadashi Udagawa, Tomomi Matsunaga |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Adoptive cell transfer
T-Lymphocytes Induced Pluripotent Stem Cells Spleen Mice SCID Mucosal associated invariant T cell Mycobacterium Immunocompromised Host Mice medicine Genetics Animals Humans Induced pluripotent stem cell Receptor Cell Proliferation Mycobacterium Infections Mucous Membrane biology Cell Differentiation Cell Biology Cellular Reprogramming Fetal Blood biology.organism_classification Sendai virus Cell biology medicine.anatomical_structure Gene Expression Regulation Immunology Molecular Medicine Female Bone marrow Reprogramming |
| Zdroj: | Cell Stem Cell. 12(5):546-558 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2013.03.001 |
| Popis: | SummaryMucosal-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|