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.

HIV, labeling, lifespan, lymphocytes, mathematical modeling, stable isotope, T cells,
Department of Gastroenterology & Hepatology

Vrisekoop, N, Drylewicz, J, van Gent, R, Mugwagwa, T, van Lelyveld, S.F.L, Veel, E, … Borghans, J.A.M. (2015). Quantification of naive and memory T-cell turnover during HIV-1 infection. AIDS, 29(16), 2071–2080. doi:10.1097/QAD.0000000000000822