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Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
Published on: January 7, 2019
Quantification of naive and memory T-cell turnover during HIV-1 infection
Nienke Vrisekoop1, Julia Drylewicz, Rogier Van Gent
1aLaboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht bTheoretical Biology and Bioinformatics, Utrecht University, Utrecht cDepartment of Gastroenterology and Hepatology, Erasmus MC Rotterdam, Rotterdam, The Netherlands dDepartment of Infectious Disease Epidemiology, Imperial College, London, UK eDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht fDepartment of Internal Medicine and Gastroenterology, Kennemer Gasthuis, Haarlem gDepartment of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center hIATEC, Academic Medical Center iDepartment of Internal Medicine, Academic Medical Center jDepartment of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands. *Nienke Vrisekoop, Julia Drylewicz, Rogier Van Gent contributed equally to this study; Rob J. de Boer, Kiki Tesselaar, José A.M. Borghans also contributed equally to this study.
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 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.
