An anti-CD45RO immunotoxin kills latently infected human immunodeficiency virus (HIV) CD4 T cells in the blood of HIV-positive persons.
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.
Saavedra-Lozano
Jesús
J
Cancer Immunobiology Center and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390-8576, USA.
McCoig
Cynthia
C
Xu
Jinbo
J
Cao
Yanying
Y
Keiser
Philip
P
Ghetie
Victor
V
Siliciano
Robert F
RF
Siliciano
Janet D
JD
Picker
Louis J
LJ
Ramilo
Octavio
O
Vitetta
Ellen S
ES
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
D004279:DNA, Viral; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens