Human and murine memory γδ T cells: Evidence for acquired immune memory in bacterial and viral infections and autoimmunity

γδ T cells are unconventional lymphocytes that could play a role in bridging the innate and adaptive immune system. Upon initial exposure to an antigen, some activated T cells become memory T cells that could be reactivated upon secondary immune challenge. Recently, subsets of γδ T cells with a restricted antigen repertoire and long-term persistence have been observed after clearance of viral and bacterial infections. These γδ T cells possess the hallmark ability of memory T cells to respond more strongly and proliferate to a higher extent upon secondary infection. Murine and primate models of Listeria monocytogenes and cytomegalovirus infection display these memory hallmarks and demonstrate γδ T cell memory responses. In addition, human and non-human primate infections with Mycobacterium tuberculosis, as well as non-human primate infection with monkeypox and studies on patients suffering from autoimmune disease (rheumatoid arthritis and multiple sclerosis) reveal memory-like responses corresponding with disease. Murine models of psoriatic disease (imiquimod) and parasite infections (malaria) exhibited shifts to memory phenotypes with repeated immune challenge. These studies provide strong support for the formation of immune memory in γδ T cells, and memory γδ T cells may have a widespread role in protective immunity and autoimmunity.