title: OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion.
abstract: Activation of resting T cells has been proposed to purge the reservoir of HIV-1-infected resting CD4+ T cells. We therefore treated three HIV-1-infected patients on antiretroviral therapy with OKT3, a CD3 monoclonal antibody, and recombinant human IL-2. Here we report the profound and partially long-lasting host responses induced by the OKT3 and IL-2 treatment. OKT3/IL-2 induced a strong but transient release of plasma cytokines and chemokines. The percentage CD4+ and CD8+ cells in the blood expressing the activation marker CD38 transiently increased to almost 100%, and in lymph nodes we "observed" a 10-fold increase in the number of dividing Ki67+ cells and increased numbers of apoptotic cells. Following OKT3/IL-2 treatment, a long-lasting depletion of CD4+ cells in the peripheral blood and lymph nodes occurred, suggesting the physical deletion of these cells. Increases in CD4+T cell numbers during the two year followup period were due mainly to increased memory cell numbers. CD8+ cells were also depleted in the blood, but less severely in lymph nodes, and returned to baseline levels within several weeks.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: van Praag
authors.forename: J M
authors.initials: JM
authors.lastname: Prins
authors.forename: M T
authors.initials: MT
authors.lastname: Roos
authors.forename: P T
authors.initials: PT
authors.lastname: Schellekens
authors.forename: I J
authors.initials: IJ
authors.lastname: Ten Berge
authors.forename: S L
authors.initials: SL
authors.lastname: Yong
authors.forename: H
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: A J
authors.initials: AJ
authors.lastname: Eerenberg
authors.forename: S
authors.initials: S
authors.lastname: Jurriaans
authors.forename: F
authors.initials: F
authors.lastname: de Wolf
authors.forename: C H
authors.initials: CH
authors.lastname: Fox
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: F
authors.initials: F
authors.lastname: Miedema
authors.forename: J M
authors.initials: JM
authors.lastname: Lange
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion / Q000379:methods; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D007376:Interleukin-2; D016853:Muromonab-CD3