Purpose of the Study. It was recently established that both acute HIV and its simian counterpart, simian immunodeficiency virus (SIV), are accompanied by dramatic and selective loss of memory CD4+ T cells. This loss has been shown to primarily occur in mucosal tissues. The extent and mechanisms underlying this depletion have not been defined. The purpose of this study was to investigate these questions in a simian model.
Methods. Eight rhesus macaque monkeys were infected with a pathogenic strain of SIV. Plasma and tissue samples were collected at various time points by biopsy and necropsy. Lymphocyte subsets were analyzed with standard flow cytometry, and T-cell–associated viral DNA was measured by a highly sensitive quantitative polymerase chain reaction assay.
Results. This study demonstrated that in this monkey model, memory CD4+ T cells are depleted in multiple tissues during acute SIV infection. In addition, the loss of these cells is explained by a massive infection of these cells by the virus. Specifically, ∼50% of these cells throughout the body are infected by SIV at the peak of infection, and most of the infected cells disappear within several days. Alternative mechanisms are not required. This depletion occurs to a similar extent in all tissues.
Conclusions. Acute immunodeficiency virus infection results in the loss of ∼50% of all memory T cells within days of infection. This and other studies strongly suggest that this loss, at least in adult animals and humans, is irreversible.
Reviewer Comments. This study confirms and extends previous findings demonstrating massive memory T-cell loss during acute HIV or SIV infection. The extent to which this loss is recoverable is likely to be very limited. Most interesting is that these authors also noted that naive T cells are highly resistant to SIV infection. These observations are particularly important for infants infected with HIV. Young infants have fewer memory CD4+ T cells, and, therefore, their loss may not be as critical in newborns. In addition, the thymus in young children may be more capable of reconstituting memory T-cell functions if HIV is completely suppressed early. Similar studies should be performed on infant laboratory animals to determine the extent to which recovery is likely in infected children.
- Copyright © 2006 by the American Academy of Pediatrics