Evidence for antigen presentation by human neutrophils

Abstract Neutrophils are the first migrating responders to sterile and infectious inflammation and act in a powerful but nonspecific fashion to kill a wide variety of pathogens. It is now apparent that they can also act in a highly discriminating fashion; this is particularly evident in their interactions with other cells of the immune system. It is clear that neutrophils are present during the adaptive immune response, interacting with T cells in complex ways that differ between tissue types and disease state. One of the ways in which this interaction is mediated is by neutrophil expression of HLA molecules and presentation of antigen to T cells. In mice, this is well established to occur with both CD4+ and CD8+ T cells. However, the evidence is less strong with human cells. Here, we assembled available evidence for human neutrophil antigen presentation. We find that the human cells are clearly able to upregulate HLA-DR and costimulatory molecules; are able to process protein antigen into fragments recognized by T cells; are able to enter lymph node T cell zones; and, in vitro, are able to present antigen to memory T cells, inducing proliferation and cytokine production. However, many questions remain, particularly concerning whether the cell-cell interactions can last for sufficient time to trigger naïve T cells. These experiments are now critical as we unravel the complex interactions between these cells and their importance for the development of human immunity.