Accelerated immune senescence and HIV-1 infection.
A recent consensus has emerged regarding the association between chronic immune activation and poor outcome in HIV-1 infection. However, its basis remains unclear. Accumulating evidence suggests that the cells of the immune system may have a limited replicative lifespan in vivo. In this context, persistent activation during chronic HIV infection may lead to an exhaustion of immune resources. This may occur at two levels: Clonal and Global. Some HIV-1-specific CD8+ T-cells start expressing the senescence marker CD57 soon after primary infection. Persistently activated HIV-1-specific T-cell clones may eventually reach stages of replicative senescence and disappear, resulting in the specific loss of CD8+ T-cell populations important to control viral replication. In addition, HIV-1 infected individuals are characterized by the accumulation of highly differentiated CD8+ and CD4+ T-cells overtime. Together with the decline of T-cell renewal capacities, this may reflect a general ageing of the lymphocyte population. Similar observations have been done in HIV non-infected elderly individuals, which suggests that premature immunosenescence occurs in HIV-1 infection, as a result of persistent immune activation.
Appay
Victor
V
Laboratoire d'Immunologie Cellulaire et Tissulaire, INSERM U543, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France. victor.appay@chups.jussieu.fr
Almeida
Jorge R
JR
Sauce
Delphine
D
Autran
Brigitte
B
Papagno
Laura
L
D000375:Aging / Q000276:immunology*; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D013997:Time Factors; D014779:Virus Replication
D015415:Biomarkers