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CD161 Defines a Transcriptional and Functional Phenotype across Distinct Human T Cell Lineages

2014; Cell Press; Volume: 9; Issue: 3 Linguagem: Inglês

10.1016/j.celrep.2014.09.045

2639-1856

Joannah R. Fergusson, Kira Smith, Vicki M. Fleming, Neil Rajoriya, Evan W. Newell, Ruth Simmons, Emanuele Marchi, Sophia Björkander, Yu-Hoi Kang, Leo Swadling, Ayako Kurioka, Natasha Sahgal, Helen Lockstone, Dilair Baban, Gordon J. Freeman, Eva Sverremark‐Ekström, Mark M. Davis, Miles P. Davenport, Vanessa Venturi, James E. Ussher, Christian B. Willberg, Paul Klenerman,

CAR-T cell therapy research

The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage.