Spatial determinates of effector and memory CD8<sup>+</sup> T cell fates*
Brigette C. Duckworth, Raymond Z. Qin, Joanna R. Groom
Abstract
Abstract The lymph node plays a critical role in mounting an adaptive immune response to infection, clearance of foreign pathogens, and cancer immunosurveillance. Within this complex structure, intranodal migration is vital for CD8 + T cell activation and differentiation. Combining tissue clearing and volumetric light sheet fluorescent microscopy of intact lymph nodes has allowed us to explore the spatial regulation of T cell fates. This has determined that short‐lived effector (T SLEC ) are imprinted in peripheral lymph node interfollicular regions, due to CXCR3 migration. In contrast, stem‐like memory cell (T SCM ) differentiation is determined in the T cell paracortex. Here, we detail the inflammatory and chemokine regulators of spatially restricted T cell differentiation, with a focus on how to promote T SCM . We propose a default pathway for T SCM differentiation due to CCR7‐directed segregation of precursors away from the inflammatory effector niche. Although volumetric imaging has revealed the consequences of intranodal migration, we still lack knowledge of how this is orchestrated within a complex chemokine environment. Toward this goal, we highlight the potential of combining microfluidic chambers with pre‐determined complexity and subcellular resolution microscopy.