an-improved-high-throughput-respiratory-syncytial-virus-rsv-micro

An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay

Respiratory syncytial virus-specific neutralizing antibodies (RSV NAbs) are an important marker of protection against RSV. A number of different assay ...

Murdoch Children'S Research Institute

The human immune system is a tightly regulated network that protects the host from disease. An important aspect of this is the balance between pro-inflammatory Th17 cells and anti-inflammatory T regulatory (Treg) cells in maintaining immune homeostasis. Foxp3+ Treg are critical for sustaining immune tolerance through IL-10 and transforming growth factor-β while related orphan receptor-γt+ Th17 cells promote immunopathology and auto-inflammatory diseases through the actions of IL-17A, IL-21 and IL-22. Therefore, imbalance between Treg and Th17 cells can result in serious pathology in many organs and tissues. Recently, certain IL-17-producing cells have been found to be protective against infectious disease, particularly in relation to extracellular bacteria such Streptococcus pneumoniae; a number of other novel IL-17-secreting cell populations have also been reported to protect against a variety of other pathogens. In this mini-review, the dual roles of Treg and Th17 cells are discussed in the context of autoimmunity and infections, highlighting recent advances in the field. Development of novel strategies specifically designed to target these critical immune response pathways will become increasingly important in maintenance of human health.

The contrasting roles of Th17 immunity in human health and disease.

Cryopreservation of blood-derived immune cells is commonly used in clinical trials to examine immunological responses. However, studies elucidating the effects of cryopreservation on peripheral blood mononuclear cell (PBMC) responses have shown inconsistent results making it difficult to draw meaningful conclusions. Therefore we sought to address this issue by comparing key innate and adaptive immune parameters between freshly-isolated and cryopreserved PBMCs from healthy adults. We examined the effect of cryopreservation on the expression of key markers on innate and adaptive immune cell populations (i.e. CD4+ and CD8+ [T cells], CD14+ [monocytes], CD19+ [B cells], CD56+ [NK cells] or CD19 + CD27+ [memory B cells]), on cytokine secretion (TNF-α, INF-γ, IL-1β, IL-10, IL-6, MCP-1 and RANTES) in cultured PBMC supernatants following stimulation with a range of Toll-like receptor (TLR) agonists, as well as on antigen-specific memory B cell enumeration by ELISpot. We found that cryopreservation had no effect on the expression of immune markers on innate and adaptive immune cells as well on the number of antigen-specific memory B cells. However, the response to TLR ligands such as FLA-ST, CpG and LPS was variable with increased cytokine production by cryopreserved PBMCs observed compared to freshly-isolated PBMCs. Our results suggest that the effect of cryopreservation on the biological response of immune cell populations needs to be carefully considered, particularly in the context of clinical studies that rely on these immune outcomes.

Jeremy Anderson

Murdoch Children'S Research Institute

An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay