Abstract
Expression of the C-type lectin-like receptor CD161 by human T cells is associated with type-17 responses, which play critical regulatory roles in immunity and inflammation at mucosal sites. However, the functions of CD161-expressing T cells in macaques, the pre-clinical model of several human diseases, remain unknown. This study examined the phenotypic and functional characteristics of CD161+ T cells in peripheral blood, mucosal tissues and lymph nodes of rhesus macaques. Majority of CD161-expressing T cells in peripheral blood and lung/intestinal mucosal tissues of rhesus macaques were found to be CD8+CD4– in phenotype. There was a significant enrichment of CD161+CD8+ T cells in the lungs and colonic mucosa (16.1%±6.6 and 16.8%±5.7) in comparison to peripheral blood (4.2%±1.2) and mesenteric lymph nodes (1.3%±0.8). Regardless of the tissue compartment, CD161+CD8+ T cells mainly comprised of γδ T cells and TCR Vα7.2+ MAIT cells (up to 80%), and displayed Th1 and Th17 cytokine responses to mitogen stimulation. Mucosal CD161+CD8+ T cells were characterized by very high expression of CD69, a recent activation marker that is preferentially expressed on tissue resident cells. Furthermore, lung and colonic mucosal CD161+CD8+ T cells showed enhanced IFN-γ, IL-17, and Perforin production in comparison to those in blood. Thus, macaque CD161+CD8+ T cells represent mucosal tissue-homing innate-like CD8+ T-cell populations with Th1/Th17 type cytokine and cytotoxic effector functions that can potentially enhance the recruitment of adaptive immune cells and control initial pathogen burden/dissemination in tissues. Analysis of their role in early immune responses to mucosal pathogens will be valuable in the design of vaccines and therapeutics.
Highlights
CD161 is a C-type lectin-like receptor that belongs to the Killer cell lectin-like receptor subfamily (KLRB1), known as NKR-P1
Similar to that reported in human CD161-expressing T cells, there was a trend of increase in CD161 median fluorescence intensity (MFI) from total T cells
Human CD161-expressing T cells have a characteristic transcriptional signature associated with innate-like function, display antiviral potential, and are enriched in tissues [7,14], suggesting that their effector functions are significant in tissue specific immune responses
Summary
CD161 is a C-type lectin-like receptor that belongs to the Killer cell lectin-like receptor subfamily (KLRB1), known as NKR-P1. CD161 is expressed by a broad range of lymphocytes, including NK cells, CD4+, CD8+, γδ+ Tcells, NKT cells, and mucosal-associated invariant T (MAIT) cells [2,3]. It acts both as an inhibitory receptor and as a co-stimulatory molecule for proliferation, cytolytic activity and IFN-γ production by NK cells and T cells [2,4,5]. Recent studies have determined the significance of CD161 expression in the type-17 effector functions of human T cells and regulation of tissue-specific immune responses [3,6,7,8]. The biological functions of the receptor in T cells including its roles in inflammation and infections remain to be fully defined
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