No monkey business: why studying NK cells in non-human primates pays off

Abstract

Human NK (hNK) cells play a key role in mediating host immune responses against various infectious diseases. For practical reasons, the majority of the data on hNK cells has been generated using peripheral blood lymphocytes. In contrast, our knowledge of NK cells in human tissues is limited, and not much is known about developmental pathways of hNK cell subpopulations in vivo. Although research in mice has elucidated a number of fundamental features of NK cell biology, mouse, and hNK cells significantly differ in their subpopulations, functions, and receptor repertoires. Thus, there is a need for a model that is more closely related to humans and yet allows experimental manipulations. Non-human primate models offer numerous opportunities for the study of NK cells, including the study of the role of NK cells after solid organ and stem cell transplantation, as well as in acute viral infection. Macaque NK cells can be depleted in vivo or adoptively transferred in an autologous system. All of these studies are either difficult or unethical to carry out in humans. Here we highlight recent advances in rhesus NK cell research and their parallels in humans. Using high-throughput transcriptional profiling, we demonstrate that the human CD56(bright) and CD56(dim) NK cell subsets have phenotypically and functionally analogous counterparts in rhesus macaques. Thus, the use of non-human primate models offers the potential to substantially advance hNK cell research.

Keywords: NK cell subpopulations; non-human primate models; rhesus macaques; transcriptional profiling.

Figure 1

Transcriptional data suggest a high degree of homology between hNK and rmNK cell subsets. (A) Principal component analysis (PCA) representation of the CD56⁺, DN, and CD16⁺ rmNK cell subsets. PC1 (horizontal) and PC2 (vertical) axes are shown. (B–D) Relative mRNA expression of genes encoding for effector proteins (B), cell surface receptors and proteins (C) and proteins associated with transcriptional control (D) are shown.

Figure 2

Comparison of rmNK and hNK cell subpopulations. Markers characterizing the distinct NK cell subpopulations are illustrated with an emphasis on molecules either indicating a more primitive stage of hematopoietic differentiation or an effector cell profile. (A) Human CD56^bright and CD56^dim NK cells are shown. (B) Rhesus CD56⁺, DN, and CD16⁺ NK cell subsets are shown.