These in vitro tests of cellular immunity detect interferon. Individuals who were once exposed to M. tuberculosis complex have lymphocytes in their blood that maintain memory for the priming TB antigen. Addition of TB antigen to blood in vitro results in rapid stimulation of memory T lymphocytes and release of interferon gamma, which is a specific marker of activation of the immune response29,30.
IGRAs have the advantage that there is no cross reactivity with prior BCG vaccination and with most environmental mycobacteria. However, overall, they offer little advantage over conventional skin testing and may be a less sensitive test in HIV co-infected. In addition, IGRAs remain expensive and are not routinely used in resource-constrained settings.