Vasorelaxant role of antigen-experienced CD8+ T cells during acute viral infection

• Main Author: Laguna Merced, Aisha
• Other Authors: Franzblau, Carl
• Language: en_US
• Published: 2021
• Subjects: Immunology
• Online Access: https://hdl.handle.net/2144/43440

Synthesis, storage and release of “neuronal” Acetylcholine (ACh) has long been studied in the context of neurons. In addition, the roles of ACh in neurotransmission, regulation of movement, heart rate, digestion and induction of vasodilation has been well-established. However, for decades now multiple studies have shown synthesis of ACh in non-neuronal cells, such as immune cells. Synthesis of ACh catalyzed by cholinesterase (ChAT) enzyme within CD4+ and CD8+ T cells in the context of viral infection has been reported. Furthermore, it has been reported that ChAT expression is induced in CD4+ and CD8+ T cells during chronic viral infection in an interleukin (IL)-21 dependent manner. Lastly, studies have demonstrated that deletion of ChAT within T cells abolishes vasodilation, and that ChAT expression is required to control chronic viral infection. However, ChAT production by CD8+ T cells in the context of acute viral infection is not well-understood. Furthermore, the kinetics of ChAT production and ACh release following acute viral infection, remains unknown. Here we show that ChAT production by CD8+ T cells is only induced following acute viral infection with Lymphocytic choriomeningitis virus (LCMV). Our results also indicate ChAT production peaks and decreases overtime throughout the course of the infection. In addition, if we introduce cognate peptide after viral clearance, production of ChAT by CD8+ T cells remains constant. Our data demonstrates that after rechallenge of CD8+ effector memory T cells the upward and downward trend in ChAT production over time does not change. Previous work from our lab has demonstrated viral infection induces expression of CX3C chemokine receptor 1 (CX3CR1) on CD8+ effector T cells and have identified 3 antiviral CX3CR1 CD8+ effector T cell subsets. We found that CX3CR1high CD8+ effector T cells remained in circulation and discovered expression of ChAT in all 3 subsets. In this study, we show the kinetics of ChAT expression in CX3CR1 CD8 effector T cells subsets following acute viral infection, peptide stimulation, and rechallenge in the memory phase. We found that most antigen-experienced CD8+ T cells producing ChAT are CX3CR1high. In parallel, we analyzed diastolic blood pressure (diastolic BP) in the animals as way of indirectly measuring vasodilation and found that a decrease in blood pressure after stimulating antigen-experienced cells with cognate peptide. Additionally, we attempted to measure vasodilation in vivo by intravascular imaging, however we only found pulsing of arterioles following antigen stimulation. We also measured ACh release in serum, but due technical issues, we were not able to reach conclusive results. Finally, we detected expression of cholinergic/acetylcholine receptor M3 (Chrm3) in arteriolar and post-capillary venular endothelial cells, but more expression of Chrm3 in post-capillary venules. Although our data indicates antigen-experienced CD8+ T cells might have a vasorelaxant role in response to acute infection, more work has to done to prove this hypothesis. === 2024-11-30T00:00:00Z