title: An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons.
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.
authors.affiliation: Cancer Immunobiology Center and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576, USA.
authors.forename: Jesús
authors.initials: J
authors.lastname: Saavedra-Lozano
authors.forename: Cynthia
authors.initials: C
authors.lastname: McCoig
authors.forename: Jinbo
authors.initials: J
authors.lastname: Xu
authors.forename: Yanying
authors.initials: Y
authors.lastname: Cao
authors.forename: Philip
authors.initials: P
authors.lastname: Keiser
authors.forename: Victor
authors.initials: V
authors.lastname: Ghetie
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: Janet D
authors.initials: JD
authors.lastname: Siliciano
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D014766:Viremia / Q000628:therapy; D017735:Virus Latency
chemical_list: D004279:DNA, Viral; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens