Cattle NK Cell Heterogeneity and the Influence of MHC Class I.
Bottom Line: Cytokine stimulation differentially influenced the transcription of five receptors at the cell population level.Using dilution cultures, we found that a further seven receptors were differentially transcribed, including five predicted to recognize MHC class I.Moreover, there was a statistically significant reduction in killer cell lectin-like receptor mRNA expression between cultures with different CD2 phenotypes and from animals with different MHC class I haplotypes.
Affiliation: The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.Show MeSH
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Mentions: Five genes showed variable mRNA expression patterns that were independent of MHC class I background (Fig. 2). NCR1 expression on CD3− cells currently defines cattle NK cells, but we observed that NCR1 transcription was not ubiquitous, and in cells from animal 982 we were not able to detect NCR1 transcription following isolation based on NCR1 expression. The activating receptor gene 2B4 was always transcribed by ex vivo NK cells but was partially or completely lost in cytokine-stimulated NK cells from eight animals. Conversely, TIM-3 was absent in the ex vivo populations from 10 of the 14 animals but was consistently transcribed by all animals after in vitro cytokine stimulation. CD8β was consistently transcribed by ex vivo and IL-2 and IL-15 in vitro stimulated NK cells, but in four animals, transcription was lost upon stimulation with IL-12/18. Only KIR3DXL6 appeared to have variable transcription with no discernible pattern (Fig. 2). Although KLRA appears differentially transcribed, two distinct allele lineages are found in cattle. We have previously genotyped this group of animals for the presence of each KLRA lineage, and these NK population differences are due to genotype rather than differential regulation.
Affiliation: The Pirbright Institute, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.