Nature Medicine
3, 533 - 540 (1997)
doi:10.1038/nm0597-533
HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapiesMark Connors1, Joseph A. Kovacs2, *, Seth Krevat1, Juan C. Gea-Banacloche1, 3, Michael C. Sneller1, Mark Flanigan1, Julia A. Metcalf1, Robert E. Walker1, Judith Falloon1, Michael Baseler4, Randy Stevens4, Irwin Feuerstein5, Henry Masur2
& H. Clifford Lane1
1Laboratory of lmmunoregulation of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11B-13, 10 Center Drive, Bethesda, Maryland 20892-1876, USA
2Clinical Center, Critical Care Medicine Department, National Institutes of Health, Building 10, Room 7D43, 10 Center Drive, Bethesda, Maryland 20892-1662, USA
3Servicio de Medicina Intema 1, Clinica Puerta de Hierreo, Madrid, Spain
4Frederick Cancer Research and Development Center, Science Application International Corporation, National Cancer Institute, Building 499, Room 7, Frederick, Maryland 21702, USA
5Clinical Center, Diagnostic Radiology, National Institutes of Health, Building 10, Room 1C660, 10 Center Drive, Bethesda, Maryland 20892-1182, USA
*J.A.K. is also considered first author of this article. Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.
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