IL-2 immunotherapy to recently HIV-1 infected adults maintains the numbers of IL-17 expressing CD4+ T (T(H)17) cells in the periphery

J Clin Immunol. 2010 Sep;30(5):681-92. doi: 10.1007/s10875-010-9432-3. Epub 2010 Jun 23.

Abstract

Little is known about the manipulation of IL-17 producing CD4+ T cells (T(H)17) on a per-cell basis in humans in vivo. Previous studies on the effects of IL-2 on IL-17 secretion in non-HIV models have shown divergent results. We hypothesized that IL-2 would mediate changes in IL-17 levels among recently HIV-1-infected adults receiving anti-retroviral therapy. We measured cytokine T cell responses to CD3/CD28, HIV-1 Gag, and CMV pp65 stimulation, and changes in multiple CD4+ T cell subsets. Those who received IL-2 showed a robust expansion of naive and total CD4+ T cell counts and T-reg counts. However, after IL-2 treatment, the frequency of T(H)17 cells declined, while counts of T(H)17 cells did not change due to an expansion of the CD4+ naïve T cell population (CD27+CD45RA+). Counts of HIV-1 Gag-specific T cells declined modestly, but CMV pp65 and CD3/CD28 stimulated populations did not change. Hence, in contrast with recent studies, our results suggest IL-2 is not a potent in vivo regulator of T(H)17 cell populations in HIV-1 disease. However, IL-2-mediated T-reg expansions may selectively reduce responses to certain antigen-specific populations, such as HIV-1 Gag.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Count
  • Cell Proliferation / drug effects
  • Drug Therapy, Combination
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1
  • Humans
  • Immunomodulation
  • Immunotherapy*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-2 / administration & dosage*
  • Interleukin-2 / therapeutic use
  • Phosphoproteins / immunology
  • T-Cell Antigen Receptor Specificity
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / pathology
  • Th17 Cells / virology
  • Viral Matrix Proteins / immunology
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Anti-Retroviral Agents
  • Antibodies, Monoclonal
  • Interleukin-17
  • Interleukin-2
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • gag Gene Products, Human Immunodeficiency Virus