Directly measured kinetics of circulating t lymphocytes in normal and hiv-1-infected humans

ABSTRACT The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique1, we report direct measurements

of circulating T-cell kinetics in normal and in HIV-1-infected humans. In healthy, HIV-1-seronegative subjects, CD4+ and CD8+ T cells had half-lives of 87 days and 77 days, respectively,

with absolute production rates of 10 CD4+ T cells/μl per day and 6 CD8+ T cells/μl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/μl), the half-life of

each subpopulation was less than 1/3 as long as those of healthy, HIV-1-seronegative subjects but was not compensated by an increased absolute production rate of CD4+ T cells. After viral

replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4+ and CD8+ T cells were considerably elevated; the kinetic basis of

increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4+ T-cell lymphopenia is due to both a shortened survival

time and a failure to increase the production of circulating CD4+ T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HIGH CD45 EXPRESSION OF CD8+ AND CD4+ T CELLS CORRELATES WITH THE SIZE OF HIV-1 RESERVOIR IN BLOOD Article Open access 24

November 2020 THE TETRASPANIN CD151 MARKS A UNIQUE POPULATION OF ACTIVATED HUMAN T CELLS Article Open access 25 September 2020 IMMUNE MOBILISING T CELL RECEPTORS REDIRECT POLYCLONAL CD8+ T

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a paradigm revisited. _Immunol. Today_ 19, 44–48 1998). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the individuals who participated in this study, as well

as Project Inform and other members of the Bay Area AIDS community for support, H.C. Lane for technical support, and R.M. Grant for his reading of the manuscript. This work was supported by

grants from the NIH, the UCSF Center for AIDS Research and SpectruMedix (to M.K.H.) and from the NIH, the UCSF Center for AIDS Research, the UCSF/Macy's Center for Creative Therapies

and the Gladstone Institute (to J.M.M.). J.M.M. is an Elizabeth Glaser Scientist supported by the Elizabeth Glaser Pediatric AIDS Foundation. An NIH Grant from the Division of Research

Resources supported the General Clinical Research Center. D.M. received funds from a Medical Research Council (UK) Traveling Fellowship. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Department of Medicine, San Francisco General Hospital University of California at, San Francisco, 94110, California , USA M. Hellerstein, R. Hoh, R. Neese, D. Macallan, S. Deeks & J.M.

McCune * Department of Nutritional Sciences, University of California, Berkeley, 94720, California, USA M. Hellerstein, D. Cesar, S. Siler, C. Papageorgopoulos & R. Neese * Gladstone

Institutes of Virology and Immunology, San Francisco General Hospital, University of California at, San Francisco , 94141-9100, California, USA M.B. Hanley, E. Wieder, D. Schmidt & J.M.

McCune * Department of Microbiology and Immunology, University of California at, San Francisco, 94110, California, USA J.M. McCune Authors * M. Hellerstein View author publications You can

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AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Hellerstein, M., Hanley, M., Cesar, D. _et al._ Directly measured kinetics of circulating T lymphocytes in

normal and HIV-1-infected humans. _Nat Med_ 5, 83–89 (1999). https://doi.org/10.1038/4772 Download citation * Received: 31 August 1998 * Accepted: 18 November 1998 * Issue Date: January 1999

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