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Updated: May 5, 2026

Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays
12:07

Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell Cytotoxic Assays

Published on: March 14, 2011

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HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28

M Roederer1, P A Raju, D K Mitra

  • 1Department of Genetics, Stanford University, California 94305-5125, USA. roederer@darwin.stanford.edu

The Journal of Clinical Investigation
|April 1, 1997
PubMed

Insights

Naive CD4 T cells resist HIV replication when stimulated via CD3/CD28, unlike memory cells. This finding supports therapies involving ex vivo expansion of CD4 T cells for HIV treatment.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human Immunodeficiency Virus (HIV) primarily targets CD4 T cells.
  • Understanding differential susceptibility of T cell subsets to HIV infection is crucial for therapeutic strategies.

Purpose of the Study:

  • To investigate the replication capacity of the T cell tropic HIV strain LAI in naive versus memory CD4 T cells.
  • To explore the mechanisms underlying differential HIV replication in CD4 T cell subsets.
  • To evaluate the potential of naive CD4 T cells for HIV therapy.

Main Methods:

  • Isolation of highly purified naive (CD45RA+CD62L+) and memory CD4 T cells using Fluorescence-Activated Cell Sorting (FACS).
  • Stimulation of T cells via cross-linking CD3/CD28 or using phytohemagglutinin (PHA).
  • Quantification of HIV LAI replication in different T cell subsets.
  • Analysis of viral coreceptor expression and transcription factor activation (NF-κB, AP-1).

Main Results:

  • HIV LAI replicated efficiently in PHA-stimulated naive and memory CD4 T cells.
  • LAI replication was significantly restricted in naive CD4 T cells stimulated via CD3/CD28, while robust in memory cells.
  • No suppression or restoration of replication was observed upon remixing naive and memory T cells.
  • Resistance in naive T cells was not linked to viral coreceptor expression or transcription factor activation.

Conclusions:

  • Naive CD4 T cells exhibit inherent resistance to productive HIV infection under specific physiological stimulation.
  • Memory CD4 T cells support robust HIV replication upon similar stimulation.
  • The proliferative capacity and resistance of naive CD4 T cells offer a rationale for ex vivo expansion and reinfusion therapies in HIV-infected individuals.

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