Quantification of naive and memory T-cell turnover during HIV-1 infection. (23rd October 2015)

• Record Type: Journal Article
• Authors: Vrisekoop, Nienke; Drylewicz, Julia; Van Gent, Rogier; Mugwagwa, Tendai; Van Lelyveld, Steven F.L.; Veel, Ellen; Otto, Sigrid A.; Ackermans, Mariëtte T.; Vermeulen, Joost N.; Huidekoper, Hidde H.; Prins, Jan M.; Miedema, Frank; de Boer, Rob J.; Tesselaar, Kiki; Borghans, José A.M.
• Is Part Of: AIDS. Volume 29:Number 16(2015)
• Publication Date: 2015-10-23
• Subjects: HIV -- labeling -- lifespan -- lymphocytes -- mathematical modeling -- stable isotope -- T cells; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000822
• Languages: English
• ISSNs: 0269-9370

Abstract

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 2 H2 O 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. Abstract : Supplemental Digital Content is available in the text