Since the CD4+CD28- phenotype is specific to HCMV infection, it is postulated that HCMV antigens expressed in GB tissues persistently stimulate TCRs and drive the expansion of CD4+ T cells that express CD57 and subsequently lose the activation marker CD28, indicating defect proliferative capacity and senescence of these cells (121, 122). Here, CD4 is linked to cytomegalovirus infection.