Interleukin-2 reconstitutes defective human immunodeficiency virus (HIV), and cytomegalovirus (CMV) specific CD8+ T cell proliferation in HIV infection

J Med Virol. 2006 Sep;78(9):1147-57. doi: 10.1002/jmv.20675.

Abstract

Recent studies indicate that a defective proliferative response of HIV-specific CD8+ T cells is associated with the lack of virologic control in chronic HIV infection in humans. The possible mechanisms that might be responsible for the reduced proliferative potential of HIV-specific CD8+ T cells and conditions conducive to the proliferation of CD8+ T cells were examined in 14 HIV-infected individuals and 7 HIV-uninfected controls using CFSE labeling and flow cytometry techniques, and analyzed data using 2 quantitative measurements: the percentages of proliferating CD8+ T cells (Tp), and the maximum number of cell divisions (Dm) after stimulation. It was found that CD8+ T cells from HIV-infected and -uninfected subjects proliferated equally well after polyclonal stimulation by phylohemagglutinin A (PHA); both groups reached a Tp of 92%-96% and a Dm of 5-8. However, in HIV-infected subjects, proliferation of HIV- and CMV-specific CD8+ T cells was significantly reduced compared to proliferation of CMV- specific CD8+ T cells from HIV-uninfected subjects. These defective proliferative responses of HIV- and CMV-specific CD8+ T cells were restored by the addition of IL-2 at the time of stimulation. These results may have implications for the design of immune modulation strategies in vivo.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division
  • Cells, Cultured
  • Chronic Disease
  • Cytomegalovirus / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Flow Cytometry
  • Fluoresceins
  • HIV Core Protein p24 / genetics
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunization
  • Interleukin-2 / immunology*
  • Leukocytes, Mononuclear
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Peptides / immunology
  • Phytohemagglutinins / immunology
  • Staining and Labeling
  • Succinimides
  • T-Cell Antigen Receptor Specificity
  • United States

Substances

  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Epitopes, T-Lymphocyte
  • Fluoresceins
  • HIV Core Protein p24
  • Interleukin-2
  • Peptides
  • Phytohemagglutinins
  • Succinimides