"Obviously the first question is, why" What's the mechanism"" Markowitz says.
A second paper, published online in the Journal of Virology, makes some headway toward an answer. By examining the viral burden of DNA and RNA in cells from the GI tract, and comparing that to cells from the peripheral blood, Markowitz, Mehandru and their collaborators determined that the mucosal lining of the GI tract carried a disproportionately heavy viral load. That means that the initial loss of CD4 T cells in that area is partially due to virus activity. But the researchers also found evidence suggesting that there are at least two more ways in which the cells were being killed off. Some of the T cells self-destruct (a process called activation-induced cell death or apoptosis), while some appear to be killed by other cytotoxic immune cells.
"These papers speak strongly to HIV pathogenesis, to HIV therapy, and to understanding how the host and virus interact," Markowitz says. However, the short and long term consequences of the persistence of this depletion remain unknown.
In the clinic, if the loss of CD4 T cells in the GI tract translates into increased incidence of colonic polyps or colorectal cancer, routine monitoring practices will have to be re-examined, with HIV-positive patients receiving colonoscopies earlier and perhaps more frequently than current recommendations allow. In the laboratory, these findings should give researchers another angle with which to approach HIV vaccines.
"What good is a vaccine going to be if you get immune responses in peripheral blood but t