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

Abstract

SummaryThe 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.

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

“…These subsets are clearly present at birth, suggesting that they are distinct populations with pre‐programmed functional differences. MAIT cells are only a small fraction of the CD161++ CD8+ T‐cell population in cord blood,83 but slowly expand with age, making up more than 90% of the CD161++ CD8+ T‐cell population in adults 11, 14. Both MAIT and non‐MAIT CD161++ CD8+ T‐cells share functional features, most notably the ability to respond to innate cytokines in the absence of TCR stimulation, due to their high expression of cytokine receptors such as IL‐18R and IL‐12R 9, 84.…”

“…Both MAIT and non‐MAIT CD161++ CD8+ T‐cells share functional features, most notably the ability to respond to innate cytokines in the absence of TCR stimulation, due to their high expression of cytokine receptors such as IL‐18R and IL‐12R 9, 84. This function is likely driven by the shared expression by MAIT and non‐MAIT CD161++ CD8+ T‐cells of the master transcription factor promyelocytic leukaemia zinc finger protein (PLZF) 14, 85…”

“…IL18R signalling induces the secretion of IFN γ in response to IL‐12+ IL‐18, compared with their respective ‘dim’ counterparts. CD161++ CD8+ T‐cells are uniformly high in IL‐18R expression regardless of whether they are MAIT cells or non‐MAIT, CD161++ V α 7·2−, cells,14 and this is already pre‐programmed in fetal and cord blood cells 83, 87. Additionally, CD56 bright NK cells are known for their proliferative capacity in response to cytokines;88 for example, liver‐resident CD49a+ NK cells have been found to express high levels of CD25, and were able to proliferate in response to low doses of IL‐2 89.…”

“…However, in recent years a number, a large fraction of the human CD8+ T‐cell population has been identified as mucosal‐associated invariant T‐cells (MAIT cells)9, 10, 11; an innate‐like T‐cell population that is classically defined by its expression of a semi‐invariant T‐cell receptor (TCR), V α 7·2‐J α 33, and restriction by the major histocompatibility complex (MHC) class Ib molecule, MHC‐class I‐related protein 1 (MR1) 12, 13. 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.…”

Lectin-like transcript 1 is a marker of germinal center-derived B-cell non-Hodgkin's lymphomas dampening natural killer cell functions

“…2D). 37 The combination of CD45RA and CCR7 is usually used to identify na€ ıve (CD45RA C CCR7 C ), terminally differentiated effector (CD45RA C CCR7 ¡ ), effector memory (CD45RA ¡ CCR7 ¡ ) and central memory (CD45RA ¡ CCR7 C ) T cells. 38 In agreement with CD161 expression pattern on T cells from the periphery, 39 CD161 expression on tonsil T cells was primarily found on effector memory and central memory T cells, with CD161 C CD8 C T cells being mostly of effector memory phenotype while CD161 C CD4 C T cells were mostly central memory T cells (Fig.…”