Tracing Antiviral CD8+ T Cell Responses Using In Vivo Imaging

Abstract

Scientists have long valued the power of in vivo observation to answer fundamental biological questions. Over the last 20 years, the application and evolution of intravital microscopy (IVM) has vastly increased our ability to directly visualize immune responses as they are occurring in vivo after infection or immunization. Many IVM strategies employ a strong multiphoton laser that penetrates deeply into the tissues of living, anesthetized mice, allowing the precise tracking of the movement of cells as they navigate complex tissue environments. In the realm of viral infections, IVM has been applied to better understand many critical phases of effector T cell responses, from activation in the draining lymph node, to the execution of effector functions, and finally to the development of tissue-resident memory. In this review, we discuss seminal studies incorporating IVM that have advanced our understanding of the biology of antiviral CD8⁺ T cells.

Figure 1.

Intravital microscopy provides unique insight into antiviral T cell priming, effector function, and memory. During primary viral infection, viral antigen (Ag) from the tissue may reach the draining lymph node (LN) after the transport of free virions in the lymph or through the migration of virus-infected cells or uninfected, viral-Ag bearing cells via the lymphatics (1). The adaptive antiviral T cell response initiates in the draining LN (2) after T cells recognize cognate viral Ag presented on nodal DCs. The DCs that prime antiviral CD4+ and CD8+ T cells are spatially separated. After activation, T cells proliferate and then egress from the LN (3) and carry out their effector functions at the site of infection (4) in a complex process that is still incompletely understand. A subset of T cells will persist after viral clearance as either central memory T cells (5) or resident memory T cells (6), which respond rapidly within to control viral infection.