CD4 down modulation on T-cells: an 'immune' checkpoint for HIV

Progressive decline of an efficient immune response during the asymptomatic phase of AIDS indicates a deletion of HIV-specific cells. The deletion of HIV-specific CD4(+) T cells may occur by direct or indirect cytopathic effects of productive infection. However, preceding cell death, several important cell surface molecules, such as MHC class I or CD4, are down modulated specifically in HIV-infected cells. Down modulation of the CD4 molecule on CD4(+) HIV-specific cells would abrogate efficient help to the cytotoxic arm of the immune response. Therefore, CD4 down modulation may represent an important checkpoint in HIV biology, conferring 'immune' protection to the pool of infected cells. Furthermore, down regulation of CD4 generates a population of infected T cells that should be considered as a possible reservoir for viral replication at all stages of the infection.