Date of Completion


Embargo Period



aging, influenza, CD4 T cells, vaccination, senescence, senolytics, flu, differentiation

Major Advisor

Dr. Laura Haynes

Associate Advisor

Dr. George Kuchel

Associate Advisor

Dr. Adam Adler

Associate Advisor

Dr. Evan Jellison

Field of Study

Biomedical Science


Doctor of Philosophy

Open Access

Campus Access


Aging greatly contributes to increased susceptibility to influenza infection. To effectively protect against influenza-related complications and mortality, a robust, yet controlled, cellular and humoral immune response is critical. CD4 T cells aid in carefully orchestrating the balance between inflammatory and anti-inflammatory influenza responses. With this research, we examine how the aged environment impacts these responses and CD4 T cell differentiation following influenza infection in aged mice. In this thesis, we show that the aging environment compromises the ability of CD4 T cells to differentiate into functional subsets, resulting in a multitude of dysregulated responses including, delayed viral clearance and prolonged inflammation. Priming CD4 T cells using vaccination, however, can significantly reduce inflammation, increase survival, and promote a balance between inflammatory CD4 T cell subsets. There is a significant reduction in TGF-bwith vaccination, which reduces the amount of regulatory CD4 T cells in aged mice, necessary to have an effective inflammatory response. TGF-breduction by neutralization reduces IFN-gin aged mice after infection. Even further, we examine how inflammatory and regulatory CD4 T cells are affected after eliminating senescent cells, major contributors to the aged environment. Using the senolytic cocktail D+Q, regulatory CD4 T cells and TGF-bare reduced, suggesting that the senescent environment could be effecting CD4 T cell responses to influenza. This research is the first examine the relationship between senescence and CD4 T cell differentiation. Collectively, this research shows the aged environment can be overcome to promote regulated influenza responses with aging.

Available for download on Wednesday, May 07, 2025