CD4 and HIV infectious disease: CD4+ T cells are essential in the setting of chronic viral infections, as demonstrated most clearly in HIV infection, where the progressive depletion of CD4+ helper T cells is accompanied by a progressive dysfunction of CD8+ T cells, which adopt an exhausted phenotype characterized by the expression of multiple inhibitory receptor such as PD-1, TIGIT, and LAG-3, the loss of proliferative and cytokine secretion capacity, and ultimately the loss of cytotoxic activity [28,29].