Spatial determinates of effector and memory CD8+ T cell fates.
Brigette C DuckworthRaymond Z QinJoanna R GroomPublished in: Immunological reviews (2021)
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 (TSLEC ) are imprinted in peripheral lymph node interfollicular regions, due to CXCR3 migration. In contrast, stem-like memory cell (TSCM ) 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 TSCM . We propose a default pathway for TSCM 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.
Keyphrases
- lymph node
- regulatory t cells
- high resolution
- dendritic cells
- single cell
- single molecule
- label free
- sentinel lymph node
- high throughput
- neoadjuvant chemotherapy
- type iii
- magnetic resonance
- oxidative stress
- working memory
- healthcare
- optical coherence tomography
- papillary thyroid
- living cells
- quantum dots
- stem cells
- cell therapy
- computed tomography
- circulating tumor cells
- antimicrobial resistance
- radiation therapy
- immune response
- human health
- tandem mass spectrometry
- climate change
- lymph node metastasis
- childhood cancer