CD28 is a necessary costimulatory molecule for T cell activation, and the CD28- T cell population is regarded as having a cytotoxic or regulatory phenotype [49]: the CD28- subset in CD8+T cells is expanded by chronic viral infection such as human cytomegalovirus, Epstein-Barr virus and human parvovirus B19 which have been implicated in ME/CFS pathogenesis [34, 50, 51]. Here, CD8A is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.