An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory.
CD4+ CD45RO+ T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4+ T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4+ T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalovirus-specific memory responses of CD8+ T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8+ T cell memory responses.
Cancer Immunobiology Center, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
J
J
Saavedra-Lozano
Y
Y
Cao
J
J
Callison
R
R
Sarode
D
D
Sodora
J
J
Edgar
J
J
Hatfield
L
L
Picker
D
D
Peterson
O
O
Ramilo
E S
ES
Vitetta
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D000922:Immunotoxins / Q000633:toxicity; D017493:Leukocyte Common Antigens / Q000276:immunology*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia / Q000188:drug therapy; D017735:Virus Latency / Q000187:drug effects
D000922:Immunotoxins; D017493:Leukocyte Common Antigens