Thesis Defense Announcement

School of Health Studies announces the Final Thesis Defense of

Alijowhara Alijeraiwi

for the Degree of Master of Science

March 04, 2022at 11:00 AM in Field House, Room: 166

Advisor: Marie van der Merwe

T cell changes induced by dietary/weight change

ABSTRACT: "Obesity is a condition that affects many people and is associated with numerous health issues and chronic diseases, including viral infections. For example, during the SARS-CoV2 epidemic, obesity emerged as a major risk for severe COVID 19. Obesity has been shown to increase T cell exhaustion resulting in loss of CD8+ T cell functions and reducing the immune system's capacity to fight infectious diseases. Exhausted T cells can be identified by the increased expression of the membrane protein Programmed Cell Death 1 (PD-1). While many studies demonstrate that a high-fat diet and an increase in weight can affect the immune system, there is limited knowledge of whether improved metabolic function through dietary change/weight loss can restore immune function. Therefore, the aim of the current studies was to assess if dietary change/weight loss in obese mice can improve immunity through reduced PD1 expression and restore activation-induced IFNγ. C57Bl/6 mice were fed a high-fat diet (HFD) (60% kcal) for 5 months to induce obesity. Half of the mice were then switched to a low-fat diet (LFD) (10 % kcal) for the next 9 weeks to induce weight loss. Switching mice to the LFD significantly reduced body weight, decreased adiposity, and improved fasting glucose levels and glucose clearance. However, there were no improvement in PD1 status with weight loss for CD4+ and CD8+ T in the spleen. As leptin is a major obesity-induced hormone that has been shown to affect immune cells, we also determine if activation of T cells in the presence of leptin would alter PD1 status. Human peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of increasing concentrations of leptin, and the levels of intracellular IFNγ and PD1 were measured using flow cytometry. Activation in the presence of leptin (100 ng) increased IFNγ production and enhanced the expression of PD1 in both CD4+ and CD8+ cells. In conclusion, we demonstrated that increased leptin concentration during activation will increase PD1 levels and therefore T cell exhaustion and that weight loss induced by a low-fat diet does not appear to improve the exhausted state."