Overview

Abstract

Elispot is the abbreviation for Enzyme-Linked ImmunoSpot. The name was deduced from the name for another immunological test, ELISA, a technique that is in parts similar to Elispot, and from the fact that spots are the actual readout of the assay. Elispot has been around for many years. It was first described in 1983 for the detection of heat-labile enterotoxin production of bacteria [1], followed by its use for the enumeration of specific antibody-secreting B cells [2]. The assay format was further adapted for the detection of cytokine-secreting cells, and remained generally almost unchanged until today [3]. The assay has gained popularity over the years with a renaissance in the mid-late 1990s, driven by the cancer and HIV research fields [4], which in turn encouraged manufacturers to improve on basic materials and reagents used for the assay to increase its reliability. Their introduction to the field, the availability of newly developed automated Elispot plate readers for the assay analysis [5], and the start of activities focused on assay standardization, harmonization, and validation further boosted Elispot to its current state as one of the most commonly used immunological assays in a wide range of fields and applications, including the research and translational fields of cancer, infectious and autoimmunity-related diseases, transplantation, basic immunology, as well as genetic diseases and AAV-based therapies, and even epidemiology and research on trauma-related injuries of various organs. Over the past decade, an average of 300–400 scientific papers were published each year referring to Elispot. With that, the question arises why Elispot has remained in its popularity and does not seem to fade away into the dungeon of outdated techniques despite the fact that new immunological as well as molecular-biological methods are constantly being introduced that allow scientists to examine the state and/or functions of the immune system and other cells, e.g., polychromatic flow cytometry, HLA multimer-peptide staining, mass cytometry (CyTOF), or T-cell receptor (TCR) sequencing, just to name a few. To answer the question, we need to look at Elispot a little closer.