CD8+ memory T cells and fatigue

Defining the role of Interferon-Gamma in local and systemic inflammation

Inflammation-associated fatigue

Systemic immune surveillance requires highly mobile immune cells with varying tissue tropisms. For example, naïve T cells (TN) circulate between lymph nodes (LNs) while effector T cells (TE) migrate to the site of infection to produce microbicidal effector molecules such as Interferon-γ (IFN-γ). After pathogen clearance a small fraction of TE converts into long-lived circulating memory T cells (TCIRCM) and tissue-resident memory T cells (TRM). Both memory T cell (TM) subsets serve as a rapid source of IFN-γ to protect the host against secondary infection. However, dysregulated IFN-γ activity is frequently associated with autoimmunity and subsequent fatigue. Whether these processes are affected by CD8+ TM-derived IFN-γ remains unclear. We will therefore focus on fatigue-associated disease models such as intestinal and CNS inflammation. Using multiple knockout mice we aim to define the contribution of migratory and sessile CD8+ TM to IFN-γ-dependent local and systemic autoimmunity and subsequent fatigue.