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Related Experiment Videos

Programmed cell death induced by HIV type 1 antigen stimulation is associated with a decrease in cytotoxic T

W K Chia1, J Freedman, X Li

  • 1Department of Microbiology, University of Toronto, Ontario, Canada.

AIDS Research and Human Retroviruses
|February 1, 1995
PubMed
Summary

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Peripheral blood mononuclear cells (PBMCs) from asymptomatic HIV+ patients showed cytotoxic T lymphocyte (CTL) activity against HIV-1 antigens. In contrast, PBMCs from AIDS patients exhibited reduced CTL activity and apoptosis, indicating immune system decline.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human immunodeficiency virus (HIV) compromises immune function.
  • Cytotoxic T lymphocyte (CTL) activity is crucial for controlling viral infections.
  • Understanding immune cell responses in HIV+ individuals is vital for therapeutic development.

Purpose of the Study:

  • To assess the immune competence of peripheral blood mononuclear cells (PBMCs) in HIV+ patients.
  • To evaluate cytotoxic T lymphocyte (CTL) activity in response to HIV-1 antigens.
  • To investigate the impact of disease progression on T cell responses.

Main Methods:

  • PBMCs from HIV+ patients (asymptomatic and AIDS) were stimulated with HIV-1 antigens in vitro.
  • Recombinant interleukin-2 (rIL-2) was used to enhance T cell responses.

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  • CTL activity was measured using HLA-A-matched EBV-transformed B cells expressing HIV-1 antigen.
  • Apoptosis and T cell receptor (TcR) phenotypes were analyzed.

    • Main Results:

    • Asymptomatic HIV+ PBMCs showed enhanced CTL activity with rIL-2 and HIV-1 antigen stimulation.
    • PBMCs from AIDS patients displayed no increased CTL activity and showed inhibition with rIL-2.
    • Inhibitory effects in AIDS patients were linked to CD8+ lymphocyte apoptosis and differential TcR phenotypes.
    • HIV-1 antigen initially induced proliferation in gamma/delta TcR-positive T cells before apoptosis.

    Conclusions:

    • Immune competence, specifically CTL activity, is preserved in asymptomatic HIV+ individuals but severely impaired in AIDS patients.
    • HIV-1 antigen stimulation can lead to apoptosis of CD8+ T cells in advanced HIV disease.
    • Differential responses of T cell subsets (gamma/delta TcR+ vs. negative) to HIV-1 antigens were observed prior to cell death.