Differential NKp30 Inducibility in Chimpanzee NK Cells and Conserved NK Cell Phenotype and Function in Long-Term HIV-1-Infected Animals

Abstract

HIV-1 infection in chimpanzees, the closest human relative, rarely leads to disease progression. NK cells contribute to the shaping of adaptive immune responses in humans and show perturbed phenotype and function during HIV-1 infection. In this study, we provide full phenotypic, molecular, and functional characterization for triggering molecules (NKp46, NKp30 NKp80, and NKG2D) on Pan troglodytes NK cells. We demonstrate that, in this AIDS-resistant species, relevant differences to human NK cells involve NKp80 and particularly NKp30, which is primarily involved in NK-dendritic cell interactions. Resting peripheral chimpanzee NK cells have low or absent NKp30 molecule expression due to posttranscriptional regulation and increase its levels upon in vitro activation. Following long-standing HIV-1 infection, peripheral NK cells in chimpanzees have conserved triggering receptor expression and display moderate phenotypic and functional decreases only once activated and cultured in vitro. These data suggest that one of the keys to successful lentivirus control may reside in part in a different regulation of NK cell-triggering receptor expression.

Baseline and Dynamic Expression of Activating NK Cell Receptors in the Control of Chronic Viral Infections: The Paradigm of HIV-1 and HCV

“…The presently discussed modulation of NCR expression (NKp30, NKp46, and NKp44) has been described also in chimpanzees (117), and thus appears to represent an innate mechanism of protection against chronic infections that is conserved in evolution and that provides inherent individual diversity in chronically infected (HIV and HCV) patients where it contributes to explain clinical divergence (Figures 1 and 2). …”

Activating NK cell receptor expression/function (NKp30, NKp46, DNAM‐1) during chronic viraemic HCV infection is associated with the outcome of combined treatment

“…HIV‐infected, AIDS‐free chimpanzees have low/absent NKp30 expression. NKp30 is, however, readily inducible upon NK cell activation 43. Interestingly, a recent report shows that NR patients already have high expression of IFN‐stimulated genes before therapy, and that standard IFN‐α‐based treatment does not upregulate IFN‐stimulated genes (ISGs).…”

Characterization of baboon NK cells and their xenogeneic activity

“…NKG2D was detected in the baboon PBMC; however, as the NKG2D + cells were predominantly CD16 − , thus likely predominantly T cells, this population was not further studied (SK, unpublished observations). A number of these surface markers, including NKp30, NKp80, and NKG2D have been identified on PBMC from long‐tailed macaque, pigtailed macaque, and/or chimpanzee [29,31,32]. We did not identify NKp30, NKp44, NKG2A, nor KIR/CD158 on the baboon PBMC (data not shown).…”

“…The small size of the baboon NK population, together with the amount of blood that can be drawn from a baboon, provided too small a number of purified baboon NK cells for further direct study, leading us to explore their expansion in vitro. Cells that have been identified as pigtailed macaque NK and chimpanzee NK have been expanded on feeder layers [29,32]. We set out to avoid the complicating use of feeder cells and found that the baboon NK cells can be grown in either RPMI or X‐vivo‐10 medium with FBS and 1000 U/ml IL‐2.…”