OKT3 and IL-2 treatment for purging of the latent HIV-1 reservoir in vivo results in selective long-lasting CD4+ T cell depletion

J Clin Immunol. 2001 May;21(3):218-26. doi: 10.1023/a:1011091300321.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Chemokines / blood
  • Cytokines / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1
  • Humans
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Depletion / methods
  • Muromonab-CD3 / adverse effects
  • Muromonab-CD3 / therapeutic use*
  • Pilot Projects
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology

Substances

  • Chemokines
  • Cytokines
  • Interleukin-2
  • Muromonab-CD3