Nature Immunology pp 1061 - 1068

Most untreated HIV-infected individuals will develop AIDS as the virus overcomes the immune system. A few individuals, however, can seemingly control infection. What distinguishes these 'long-term non-progressors' from most HIV-infected patients? In Nature Immunology, scientists have now identified immune response differences that could explain why these individuals control HIV-infection for many years.

Mark Connors and colleagues from the National Institutes of Health, USA, compared the ability of CD8 T cells to respond to HIV-infected cells taken from the same HIV-infected individual. CD8 T cells from long-term non-progressors and patients with progressive disease both produce interferon-gamma, a protein that fights virus infections. However, HIV-specific CD8 T cells from long-term non-progressors could divide more rapidly and to a greater extent compared to CD8 T cells taken from progressors. Importantly, the capacity to divide was tightly coupled to perforin expression, a protein that is known to kill virus-infected cells. These data define qualitative parameters that could account for the ability of long-term non-progressors to restrict HIV replication and also suggest that HIV escapes immunologic control in most individuals by deregulating cell cycle and restricting perforin expression in CD8 T cells.