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Mechanisms associated with defective TH1 cytokine production in HIV infection

N Rodriguez1, N Yano, E Eylar

  • 1Ponce School of Medicine AIDS Research Program, Puerto Rico 00732, USA.

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|February 4, 1998
PubMed

Insights

Human immunodeficiency virus type 1 (HIV-1) infection alters T-cell cytokine production. HIV-1 infection increases CD8 T-cell cytokine output while decreasing CD4 T-cell interferon-gamma production.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) infection profoundly impacts the immune system, particularly T-cell subsets.
  • Understanding the functional changes in CD4 and CD8 T-cells is crucial for comprehending HIV-1 pathogenesis and immune dysfunction.

Purpose of the Study:

  • To analyze qualitative and quantitative changes in immune functions of T-cell subsets during HIV-1 infection.
  • To investigate the production of T(H)1 cytokines, specifically interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), by CD4 and CD8 T-cells.

Main Methods:

  • Flow cytometric assessment of intracytoplasmic cytokines in T-cell subsets.
  • Activation of peripheral blood mononuclear cells (PBMC) from both healthy and HIV-1-infected individuals in culture.
  • Isolation of CD4 T-cells using a cell sorter (FACSCalibur) for further analysis.

Main Results:

  • In HIV-1-infected individuals (HIV+PBMC), an increased proportion of CD8 T-cells produced IL-2 and IFN-gamma compared to normal PBMC.
  • Production of IFN-gamma by HIV+CD4 T-cells was significantly reduced.
  • IL-2 and tumor necrosis factor-alpha (TNF-alpha) production by HIV+CD4 T-cells remained relatively intact in early to moderate stages of the disease.
  • Isolated normal CD4 T-cells produced IL-2 and TNF-alpha, but required accessory cells for full IFN-gamma production.

Conclusions:

  • HIV-1 infection alters the cytokine production profiles of both CD4 and CD8 T-cell subsets.
  • The study highlights a shift in immune function, with increased CD8 T-cell activity and impaired CD4 T-cell IFN-gamma response.
  • Further research is needed to identify accessory cells critical for normal CD4 T-cell IFN-gamma production.

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