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An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons.
Authors:Jesús Saavedra-Lozano  Cynthia McCoig  Jinbo Xu  Yanying Cao  Philip Keiser  Victor Ghetie  Robert F Siliciano  Janet D Siliciano  Louis J Picker  Octavio Ramilo  Ellen S Vitetta
Affiliation:Cancer Immunobiology Center and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576, USA.
Abstract:
Highly active antiretroviral therapy has decreased the morbidity and mortality of human immunodeficiency virus (HIV) infection, but latently infected cells remain for prolonged periods. CD4(+) CD45RO(+) T cells are a major latent virus reservoir in HIV-infected persons. Replication-competent, latently HIV-infected T cells can be generated in vitro by infecting peripheral blood mononuclear cells with HIV and then eliminating the HIV-producing cells with an anti-CD25 immunotoxin (IT). The CD25(-) latently infected cells then can be eliminated with an anti-CD45RO IT. This study determined whether this IT also could kill latently infected CD4 T cells from HIV-infected persons with or without detectable plasma viremia. The results show that ex vivo treatment of cells from HIV-positive persons by anti-CD45RO IT reduces the frequency of both productively and latently infected cells. In contrast, CD4(+) CD45RA(+) naive T cells and a proportion of CD4(+) CD45RO(lo) memory T cells are spared.
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