Abstract

Despite extensive use of nonhuman primates as models for infectious diseases and reproductive biology, imprecise phenotypic and functional definitions exist for natural killer (NK) cells. This deficit is particularly significant in the burgeoning use of small, less expensive New World primate species. Using polychromatic flow cytometry, we identified peripheral blood NK cells as CD3-negative and expressing a cluster of cell surface molecules characteristic of NK cells (i.e., NKG2A, NKp46, NKp30) in three New World primate species – common marmosets, cotton-top tamarins, and squirrel monkeys. We then assessed subset distribution using the classical NK markers, CD56 and CD16. In all species, similar to Old World primates, only a minor subset of NK cells was CD56+, and the dominant subset was CD56–CD16+. Interestingly, CD56+ NK cells were primarily cytokine-secreting cells, whereas CD56–CD16+ NK cells expressed significantly greater levels of intracellular perforin, suggesting these cells might have greater potential for cytotoxicity. New World primate species, like Old World primates, also had a minor CD56–CD16– NK cell subset that has no obvious counterpart in humans. Herein we present phenotypic profiles of New World primate NK cell subpopulations that are generally analogous to those found in humans. This conservation among species should support the further use of these species for biomedical research.

Highlights

  • In primates, there are two major arms of the immune system: a) antigen-specific adaptive immunity and b) antigen-independent innate immunity

  • Using up to 8-color flow cytometry we identified a number of cross-reactive antibodies to natural killer (NK) cell and lineage markers that could be used in these species (Figure S1)

  • In addition to NK cell-specific markers we examined a number of cell-surface markers that are associated with NK cell development, trafficking and activation (Figure 1B)

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Summary

Introduction

There are two major arms of the immune system: a) antigen-specific adaptive immunity and b) antigen-independent innate immunity. The primary effector cells of the innate immune system are natural killer (NK) cells, which can have both cytotoxic and cytokine-based regulatory functions. The first signal is an interaction with cell-surface MHC, which would be expressed on healthy cells, but lost on many virus-infected or stressed cells. A second signal can involve so-called natural cytotoxicity receptors (NCRs) including NKG2a, NKp30, NKp44, and NKp46, which can be inhibitory or activating [10,11]. In recent years attention has been more focused on MHC interactions with killer immunoglobulin-like receptors (KIRs), a polygenic family of NK cell surface receptors that appear to mediate NK cell activation and cytolysis in humans and nonhuman primate species, but are absent in other mammals [11–

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