Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

Abstract

Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

Distinct human circulating NKp30 + FcεRIγ + CD8 + T cell population exhibiting high natural killer-like antitumor potential

“…Here, we uncovered a distinct population of CD8 + T cells expressing NKp30 in the peripheral blood of healthy individuals. This population exhibited a naive phenotype, did not coexpress CD56, KIR2DL2/3, or other NCRs, and displayed a broad, diverse TCR repertoire, being distinct from other previously described circulating NK receptor-expressing CD8 + T cell populations such as KIR + CD8 + T cells (24). We revealed IL-15 as a signal capable of de novo inducing NKp30 on CD8 + T cells and driving the acquisition of a potent antitumor activity.…”

“…1E), reinforcing them as a population distinct from other NK-like CD8 + T cells. Moreover, previously described NK receptor-expressing CD8 + T cells are often characterized by an effector memory phenotype, being enriched within virusspecific T cells (24). In contrast, the NKp30 + CD8 + T cell population in peripheral blood displayed a CCR7 + CD45RA + CD28 + expression indicative of a naive phenotype (Fig.…”

Differential Effect of Cytomegalovirus Infection with Age on the Expression of CD57, CD300a, and CD161 on T-Cell Subpopulations

“…Additionally, their definition of NKT-like cells differs from ours as it is based only on CD3 and CD56 expression, not including CD8 [for review of NKT-like cells nomenclatures, see Ref. (55)]. In our previous work, regarding NKT-like cell number and functionality in the context of CMV infection and age, we show that the percentage of NKT-like cells is not affected by CMV infection in young CMV individuals, but rather with the combined effect of both age and CMV latent infection (49).…”

NKT-like cells reveal higher than T lymphocytes expression of cellular protective proteins HSP70 and SOD2 and comparably increased expression of SIRT1 in the oldest seniors

“…NKT-like cells are "non-classical", "CD1d-independent" natural killer T cells which represent highly differentiated, conventional T cells coexpressing several NK-associated receptors (NKRs) such as CD56, CD161, CD16, CD94, CD57 [1][2][3]. They refer to the original definition of Natural Killer T (NKT) cells.…”