Quantification of naive and memory T-cell turnover during HIV-1 infection

Background:In HIV infection, the homeostasis of CD4(+) and CD8(+) T cells is dramatically disturbed, and several studies have pointed out that T-cell turnover rates are increased. To understand how the CD4(+) and CD8(+) T-cell pools are affected, it is important to have quantitative insights into the lifespans of the cells constituting the different T-lymphocyte populations.Methods:We used long-term in-vivo (H2O)-H-2 labeling and mathematical modeling to estimate the average lifespans of naive and memory CD4(+) and CD8(+) T cells in untreated (n=4) and combination antiretroviral therapy-treated (n=3) HIV-1-infected individuals.Results:During untreated chronic HIV-1 infection, naive CD4(+) and CD8(+) T cells lived on average 618 and 271 days, whereas memory CD4(+) and CD8(+) T cells had average lifespans of 53 and 43 days, respectively. These lifespans were at least three-fold shorter than those in healthy controls (n=5). In patients on effective combination antiretroviral therapy with total CD4(+) T-cell counts in the normal range, we found that naive CD4(+) and CD8(+) T-cell lifespans had not completely normalized and were still two-fold shortened.Conclusion:The average lifespan of both naive and memory CD4(+) and CD8(+) T cells decreased during untreated chronic HIV-1 infection. Although the turnover of the memory T-cell populations nearly normalized during effective treatment, the turnover of naive CD4(+) and CD8(+) T cells did not seem to normalize completely.