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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
09:26

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Published on: October 15, 2013

CD4 on CD8(+) T cells directly enhances effector function and is a target for HIV infection

Scott G Kitchen1, Nicole R Jones, Stuart LaForge

  • 1Department of Medicine and Microbiology, David Geffen School of Medicine, University of California, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 3, 2004
PubMed

Insights

The CD4 molecule has a direct role in CD8(+) T cell function, impacting immune responses. HIV infection of CD8(+) T cells expressing CD4 impairs their function and contributes to immunodeficiency.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • The CD4 molecule is traditionally associated with helper T cell function.
  • The role of CD4 on CD8(+) T cells has been less understood.

Purpose of the Study:

  • To investigate the function of de novo expressed CD4 on CD8(+) T lymphocytes.
  • To determine the impact of CD4 expression on CD8(+) T cell effector functions and HIV infection.

Main Methods:

  • Purification and costimulation of CD8(+) T lymphocytes.
  • Analysis of CD4 expression, IFN-gamma, and Fas ligand.
  • Assessment of HIV infection and its effects on CD8(+) T cell responses.

Main Results:

  • Costimulation induced de novo CD4 expression on CD8(+) T cells.
  • CD4 expression directly modulated IFN-gamma and Fas ligand in CD8(+) T cells.
  • HIV infection of CD4-expressing CD8(+) T cells led to CD4 down-regulation and impaired effector functions.

Conclusions:

  • CD4 plays a direct, previously unrecognized role in CD8(+) T cell function.
  • CD8(+) T cells expressing CD4 serve as a potential reservoir for HIV.
  • Impaired CD8(+) T cell responses due to HIV infection may contribute to immunodeficiency.

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