|EDER, JORDAN - Iowa State University|
Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/2/2022
Publication Date: 4/12/2022
Citation: Eder, J.M., Sacco, R.E. 2022. Ex vivo activated CD4+ T cells from young calves exhibit Th2-biased effector function with distinct metabolic reprogramming compared to adult cows. Veterinary Immunology and Immunopathology. 248. Article 110418. https://doi.org/10.1016/j.vetimm.2022.110418.
Interpretive Summary: The naïve immune system of young calves makes them more susceptible to infection compared to adult cattle. As maternal passive immunity wanes at 6-8 weeks, young calves must rely on their own developing immune system for protection against infectious agents. Our study examines how the developing immune system of calves impacts the function of a specific subset of white blood cells in young calves compared to these cells from a fully mature immune system of adult cows. The data shows that there are differences in the responsiveness of these white blood cells between animals of differing ages. We would suggest that the altered function of white blood cells in calves may provide a partial explanation for their increased susceptibility to infection.
Technical Abstract: The naïve immune system of young calves makes them more susceptible to infection compared to adult cattle. As maternal passive immunity wanes at 6-8 weeks, young calves must rely on their own developing immune system for protection against pathogens. Typically, an infection in the young induces a T cell-mediated response, which skews towards a Th2 phenotype and result in a reduced effector response. Our study examines the implications this transitional period of immunocompetency has on cellular metabolism in young calves, focusing on effector function of CD4+ T cells in comparison to those from adult cows. Results from sorted CD4+ T cells from young calves and adult cows activated by a-CD3:a-CD28, show that young calves exhibit a greater propensity to produce the Th2 cytokine, IL-4, in comparison to IFN-' (*p<0.05). Overall, CD4+ T cells from calves produce lower levels of cytokines compared to cells from adult cows. Concomitantly, cells from young calves and adult cows show similar activation-induced cell surface marker expression. Metabolically, activated CD4+ T cells from young calves show greater utilization of both mitochondrial respiration, measured by oxygen consumption rate (OCR), and aerobic glycolysis, measured by extracellular acidification rate (ECAR). Further, CD4+ T cells from young calves have increased mRNA expression of genes associated with specific pathways of metabolism and metabolic signaling in comparison to adult cows. The distinct metabolic phenotype and associated gene expression in activated CD4+ T cells may be intrinsic drivers of the Th2-biased response by young calves. However, an increased proportion of CD4+ RTEs in young calves may further contribute to the altered effector function.