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

Abstract

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 2H2O 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.