CD4 and HIV infectious disease: In contrast to acute infection, in chronic untreated HIV infection and malignant states however, chronic antigen stimulation can lead to sustained immune activation and inflammation resulting in elevated expression of CPI molecules on effector T cells with dampened immunity manifesting as functional unresponsiveness of the immune system [18, 19] and reduced effector function of CD4 and CD8 T cells [8, 20, 21].