Maria Vono

Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans. However, whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as CD33⁺ low-density neutrophils. Importantly, both M-MDSCs and PMN-MDSCs showed suppression of T cell proliferation in vitro. The frequency of circulating MDSCs rapidly and transiently increased 24 h after vaccine administration. M-MDSCs infiltrated the vaccine injection site, but not vaccine-draining lymph nodes. This was accompanied by upregulation of genes relevant to MDSCs such as arginase-1, IDO1, PDL1, and IL-10 at the injection site. MDSCs may therefore play a role in locally maintaining immune balance during vaccine-induced inflammation.

Key Points: Neutrophils can present cognate antigens to antigen-specific memory CD4+ T cells. MHC-II and costimulatory molecules are induced on neutrophils in the presence of antigen and antigen-specific memory CD4+ T cells.

Significance: Release of endogenous danger signals has been found to be a key mechanism of many conventional, broadly used adjuvants. Yet extracellular ATP has so far not been linked to vaccination success. Here we show that ATP release from muscle is crucial for the mechanism of action of the vaccine adjuvant MF59, leading to efficient CD4 T-cell priming and high antibody titers.