CD161intCD8+ T cells: a novel population of highly functional, memory CD8+ T cells enriched within the gut

Abstract

The C-type lectin-like receptor CD161 is expressed on lymphocytes found in human gut and liver, as well as blood, especially Natural Killer cells, T helper 17 cells and a population of unconventional T cells known as Mucosal Associated Invariant T (MAIT) cells. The association of high CD161 expression with innate T cell populations including MAIT cells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including anti-viral populations, which display a memory phenotype. These memory CD161int CD8+ T cells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterised by enhanced polyfunctionality, increased levels of cytotoxic mediators and high expression of the transcription factors T-bet and Eomesodermin. Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against Hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T cell populations in humans. Since induction of such responses represents a major aim of T cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

“…Resting CD161++ CD8+ T‐cells, in particular the MAIT cells, express no GrB and little perforin, and instead are uniquely enriched for GrK expression 90. In turn, CD161+ CD8+ T‐cells are enriched for GrB and perforin expression, even compared with their CD161− CD8+ T‐cell counterparts 16. The GrK+ GrB− perforin low phenotype of CD161++ CD8+ T‐cells was similar to the phenotype of CD56 bright NK cells (Fig.…”

“…Thus, both CD56 dim NK cells and CD161+ CD8+ T‐cells are enriched for Eomes+T‐bet high cells,16, 107 while CD56 bright NK cells have an Eomes+T‐bet low phenotype,107 which is mirrored by CD8+ MAIT cells 108. Of note, CD161+ CD8+ T‐cells express higher levels of GrB and perforin even compared with their CD161− CD8+ T‐cell counterparts, although both populations contain similar frequencies of effector memory T‐cells and terminally differentiated CD8+ T‐cells 16…”

“…These cells share a functional phenotype with a family of other CD8+ T‐cells that express high levels of the C‐type lectin‐like receptor CD161 14. CD161 expression divides the CD8+ T‐cell population into three distinct functional subsets 15, 16. These subsets show varying degrees of innate (or NK‐like) activity according to their CD161 expression – thus CD161 expression can act as a marker of ‘innateness’ in T‐cell populations.…”

MDR1 in immunity: friend or foe?

“…74 In addition, xenobiotic resistance of mucosal-associated invariant T cells (MAIT) CD8 + T cells (TCR Vα7.2 + ) has been associated to their MDR1 expression. These MAIT also express high levels of CD161 and secrete IL-17A or both IFN-γ and IL-17A, displaying Tc17 and Tc1.17-like phenotypes.…”

Maximal exercise increases mucosal associated invariant T cell frequency and number in healthy young men

“…Moreover, there are at least two distinct populations of CD8 + T lymphocytes: cytotoxic T lymphocytes (CTL) that respond to viral peptide presentation (Zhang and Bevan 2011) and MAIT cells that respond predominately to bacteria (Chen et al 2017;Dusseaux et al 2011;Gold et al 2010). It has been shown that ~10% of CD8 + lymphocytes have now been identified as MAIT cells by virtue of Vα7.2 and CD161 hi expression (Cosgrove et al 2013;Dusseaux et al 2011;Fergusson et al 2016;Walker et al 2012). This calls into question previous work that has failed to exclude Vα7.2 + CD161 + cells from their CTL analysis.…”