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Related Experiment Videos

Naive CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells.

M Mengozzi1, M Malipatlolla, S C De Rosa

  • 1Department of Genetics, Stanford University, Stanford, CA 94305-5318, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 20, 2001
PubMed
Summary
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Naive CD4 T cells can suppress HIV replication in memory cells through mechanisms independent of CCR5. This finding offers new insights into controlling viral spread in HIV-infected patients.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • T cell expansion ex vivo using anti-CD3/CD28 antibodies typically suppresses HIV replication.
  • This suppression was previously attributed to CCR5 down-regulation and chemokine up-regulation.

Purpose of the Study:

  • To investigate the mechanisms of HIV replication suppression in different CD4 T cell subsets.
  • To determine if HIV suppression is dependent on CCR5 in purified memory CD4 T cells.

Main Methods:

  • Stimulation of CD4 T cells (total, naive, and CD62L(-) memory subsets) with anti-CD3/CD28 or anti-CD3/B7.1 antibodies.
  • Analysis of HIV replication, CCR5 expression, and chemokine ligand secretion.
  • Co-culture experiments with different T cell subsets.

Related Experiment Videos

Main Results:

  • HIV replication suppression was incomplete in purified CD62L(-) memory CD4 T cells despite CCR5 down-regulation.
  • Addition of naive or CD62L(+) memory CD4 T cells inhibited viral replication in CD62L(-) cells.
  • Suppression was achieved with strong anti-CD3/B7.1 stimulation, not solely bead-bound anti-CD3/CD28.

Conclusions:

  • Naive CD4 T cells express inhibitory mechanisms that suppress R5 HIV replication.
  • These inhibitory mechanisms are independent of CCR5-binding chemokines.
  • CD28 costimulation can induce potent HIV suppression mediated by naive CD4 T cells.