Loss of DNAM-1 contributes to CD8+ T-cell exhaustion in chronic HIV-1 infection.
Cella M., Presti R., Vermi W., Lavender K., Turnbull E., Ochsenbauer-Jambor C., Kappes JC., Ferrari G., Kessels L., Williams I., CHAVI Clinical Core B None., McMichael AJ., Haynes BF., Borrow P., Colonna M., NIAID Center for HIV/AIDS Vaccine Immunology None.
The hallmark of chronic viral infections is a progressive exhaustion of antigen-specific CD8(+) T cells that leads to persisting viral replication. It is generally believed that exhaustion is a consequence of the accumulation of multiple inhibitory receptors on CD8(+) T cells that makes them dysfunctional. Here, we show that during human chronic HIV-1 infection, a CD8(+) T-cell positive costimulatory pathway mediated by DNAX-activating molecule-1 is also disrupted. Thus, DNAX-activating molecule-1 downregulation on CD8(+) T cells aggravates the impairment of CTL effector function in chronic HIV-1 infection.