Degree Type

Dissertation

Date of Award

2019

Degree Name

Doctor of Philosophy

Department

Veterinary Microbiology and Preventive Medicine

Major

Immunobiology

First Advisor

Randy E. Sacco

Second Advisor

Cathy L. Miller

Abstract

Immunometabolism is a growing field and examines the effects cellular metabolism has on driving the immune response. T cell function is impacted by the changes in bioenergetics, as metabolism is intricately linked to activation signals intra- and extracellularly, nutrient acquisition, cell cycle progression and proliferation, and overall the induction of a productive effector response. This dissertation interrogates the role immunometabolism plays in CD4+ T cells from dairy cattle during the complete lactation cycle (early lactation to the dry period), as well as its role in the maturation of the CD4+ T cell response in the calf and how that compares to the adult animal.

During the dynamic process of lactation and pregnancy, dairy cattle exhibit various levels of disease susceptibility. Substantial literature indicates a reduced function of innate immunity in early lactating cows, a time when animals are most susceptible to infection. Data shown in Chapter 2 suggests that adaptive immune responses are also reduced during early lactation. CD4+ T cells, a critical cell type in the effector and memory immune response, were shown to have decreased cytokine production, as well as an altered metabolic phenotype in comparison to cells from dry cows and cows later in lactation.

Additionally, an examination of the altered effector function exhibited by calf CD4+ T cells, as anticipated, produced less cytokines, but exhibited a propensity to produce Th2-driven cytokine IL-4 rather than Th1-driven cytokine IFN-γ. Polyclonal activation of CD4+ T cells from calves induced a unique metabolic phenotype with both mitochondrial respiration and aerobic glycolysis increasing, characteristic of the metabolic phenotype of Th2 cells. Upon activation, we also show an increase in glycolytic genes and aerobic glycolysis, greater than that from adult cows. Additionally, in comparison to adult cows, we show young calves have a greater proportion of recent thymic emigrants (RTEs), an immature t cell population shown to have dampened effector and metabolic functions. However, the complete contribution of RTEs to the altered metabolic reprogramming and dampened effector function of CD4+ T cells from young calves remains to be elucidated

In conclusion, CD4+ T cells from dairy cattle exhibit differential metabolic phenotypes during activation that can be attributed to physiological status, as well as development and the maturation of the immune system.

Copyright Owner

Jordan Marie Eder

Language

en

File Format

application/pdf

File Size

189 pages

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