Intraepithelial T cells diverge by intestinal location as pigs age

Authors: Wiarda, Jayne; Trachsel, Julian; Bond, Zahra; Byrne, Kristen; GABLER, NICHOLAS - Iowa State University; Loving, Crystal

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2020
Publication Date: 6/15/2020
Citation: Wiarda, J.E., Trachsel, J.M., Bond, Z.F., Byrne, K.A., Gabler, N.K., Loving, C.L. 2020. Intraepithelial T cells diverge by intestinal location as pigs age. Frontiers in Immunology. 11:1139. https://doi.org/10.3389/fimmu.2020.01139.
DOI: https://doi.org/10.3389/fimmu.2020.01139

Interpretive Summary: Immune cells located in the lining of the intestinal tract are some of the earliest immune cells to populate the intestine, making them important in shaping early-life intestinal health with impacts on long-term overall health. Early in life pigs undergo intestinal distress from weaning when they are separated from their mothers, undergo a diet change, and are transferred into a new environment. When weaning occurs, the intestinal immune system is not yet fully developed, and the characteristics of immune cells in the intestinal lining following weaning has not been explored. In the current study, results showed immune cells in the intestinal lining were similar between intestinal locations in younger, more recently weaned pigs but became more different between intestinal locations as pigs continued to age and the immune system became more fully developed. Collectively, these data indicate immune cell populations in the intestinal lining continue to develop after weaning, and early life events may affect how these cells develop. This is important because immune cells in the intestinal lining can impact intestinal and overall pig health. Producers may use this data to consider how intervention strategies implemented early in life may impact pig intestinal health, overall health, and/or market performance.

Technical Abstract: T cells resident within the intestinal epithelium play a central role in barrier integrity and provide a first line of immune defense. Intraepithelial T cells (IETs) are among the earliest immune cells to populate and protect intestinal tissues, thereby giving them an important role in shaping gut health early in life. In pigs, IETs are poorly defined, and their maturation in young pigs has not been well studied. Given the importance of IETs in contributing to early life and long-term intestinal health through interactions with epithelial cells, the microbiota, and additional environmental factors, a deeper characterization of IETs in pigs is warranted. The objective of this study was to analyze age- and intestinal location-dependent changes in IETs across multiple sites of the small and large intestine in pigs between 4 and 8 weeks of age. IETs increased in abundance over time and belonged to both gamma delta and alpha beta T cell lineages. Similar compositions of IETs were identified across intestinal sites in 4-week-old pigs, but compositions diverged between intestinal sites as pigs aged. CD2 plus CD8alpha plus gamma delta T cells and CD4-CD8 alpha plus alpha beta T cells comprised greater than 78 percent of total IETs at all intestinal locations examined. Greater percentages of gamma delta IETs were present in large intestine compared to small intestine in older pigs. Small intestinal tissues had greater percentages of CD2 plus CD8 alpha - gamma delta IETs, while CD2 plus CD8 alpha plus gamma delta IET percentages were greater in the large intestine. Percentages of CD4-CD8 alpha plus alpha beta IETs increased over time across all intestinal sites. Moreover, percentages of CD27 plus cells decreased in ileum and large intestine over time, indicating increased IET activation. Percentages of CD27 plus cells were also higher in small compared to large intestine at later timepoints. Results herein emphasize 4 to 8 weeks of age as a critical window of IET maturation and suggest strong associations between intestinal location and age with IET heterogeneity in pigs.