Transient inhibition of type I interferon enhances CD8 T cell stemness and vaccine protection.

Unlabelled: Developing vaccines that promote CD8 T cell memory is a challenge for infectious disease and cancer immunotherapy. TCF-1 stem cell-like memory T (T ) cells are important determinants of long-lived memory. Yet, the developmental requirements for T formation are unclear.

Spatial determinates of effector and memory CD8 T cell fates.

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.

Tumor-derived MMPs regulate cachexia in a Drosophila cancer model.

Cachexia, the wasting syndrome commonly observed in advanced cancer patients, accounts for up to one-third of cancer-related mortalities. We have established a Drosophila larval model of organ wasting whereby epithelial overgrowth in eye-antennal discs leads to wasting of the adipose tissue and muscles. The wasting is associated with fat-body remodeling and muscle detachment and is dependent on tumor-secreted matrix metalloproteinase 1 (Mmp1).

Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.

T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate. After viral infection, we demonstrated that CD8 effector T cell differentiation is associated with positioning at the lymph node periphery.

Conversations that count: Cellular interactions that drive T cell fate.

The relationship between the extrinsic environment and the internal transcriptional network is circular. Naive T cells first engage with antigen-presenting cells to set transcriptional differentiation networks in motion. In turn, this regulates specific chemokine receptors that direct migration into distinct lymph node niches.

Self-assembling influenza nanoparticle vaccines drive extended germinal center activity and memory B cell maturation.

Protein-based, self-assembling nanoparticles elicit superior immunity compared with soluble protein vaccines, but the immune mechanisms underpinning this effect remain poorly defined. Here, we investigated the immunogenicity of a prototypic ferritin-based nanoparticle displaying influenza hemagglutinin (HA) in mice and macaques. Vaccination of mice with HA-ferritin nanoparticles elicited higher serum antibody titers and greater protection against experimental influenza challenge compared with soluble HA protein.