CD4+ CD25+ Foxp3+ Porcine Natural Regulatory T Cells Induced by Helminth Infection Display a Functionally Suppressive Immunomodulatory Phenotype

Abstract

CD4+/CD25+/Foxp3+ natural regulatory T cells (nTregs) limit immune responses to helminth infection and reduce inflammatory responses in rodent models. The phenotype of human nTregs is fairly well defined; but their role in immunity is largely unknown. We hypothesized that the phenotype of pig nTregs would be closer to human nTregs as compared to rodents due to greater overall immunological similarity. nTregs were characterized in pigs infected with Ascaris suum. We observed that the basal level of circulating nTregs in PBMCs closely resembled that of humans with approximately 2% of CD4+ T cells expressing CD25 (IL‐2Ra) and Foxp3. Like human nTregs, Con A‐stimulation of PBMCs resulted in higher FoxP3 mRNA and protein expression. Ascaris infection induced a consistently higher amount of PBMC CD4+/CD25+/FOXP3+ cells at 7, 14 and 21 days after infection as larvae migrated through the liver, lungs, and small intestine. Surface expression of CD25 was significantly higher in nTregs from Ascaris‐infected pigs. Infection with Ascaris also enhanced the transcription of CTLA4, PD1, and ICOS. Significant Ascaris‐induced enhancement of Con A‐stimulated PBMC mRNA expression of Foxp3, IL‐10 and TGF‐beta was also observed. These data provide the first characterization of nTregs in the pig during helminth infection and support a role for activated Tregs during Ascaris infection of its natural host. Funded by ARS/USDA.