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Regulatory T Cells Diminish HIV Infection in Dendritic Cells - Conventional CD4(+) T Cell Clusters

Maria E Moreno-Fernandez1, Jara J Joedicke2, Claire A Chougnet3

  • 1Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation , Cincinnati, OH , USA ; Immunology Graduate Program, College of Medicine, University of Cincinnati , Cincinnati, OH , USA.

Frontiers in Immunology
|May 22, 2014
PubMed

Insights

Regulatory T cells (Treg) reduce HIV infection by disrupting immunological synapses (IS) between dendritic cells (DCs) and T cells. This Treg-mediated interference limits viral spread, potentially benefiting hosts during early HIV infection.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Immunological synapses (IS) between dendritic cells (DCs) and conventional T cells (Tcon) are crucial for immune responses and HIV-1 transmission.
  • Regulatory T cells (Tregs) modulate DC-Tcon interactions, suggesting a potential role in controlling HIV infection.

Purpose of the Study:

  • To investigate whether Tregs can interfere with HIV infection transmitted from DCs to Tcon.
  • To elucidate the mechanisms by which Tregs affect DC-Tcon IS and subsequent HIV transmission.

Main Methods:

  • A model using monocyte-derived DCs infected with R5-HIV, co-cultured with Tcon in the presence or absence of autologous Tregs at a physiological ratio (1:10).
  • Analysis of IS quality, actin polymerization, DC maturation, and HIV particle trafficking to the IS.
  • Assessment of Treg effector molecules, including CD152 and cyclic adenosine monophosphate (cAMP).

Main Results:

  • Tregs significantly reduced HIV infection within DC:Tcon clusters.
  • Tregs diminished actin polymerization and DC maturation, altering IS quality.
  • Tregs decreased the trafficking of HIV particles to the IS.
  • CD152 and cAMP were identified as critical Treg effector molecules, with blockade abolishing Treg activity.

Conclusions:

  • Tregs can effectively reduce HIV dissemination by impairing the formation and function of the immunological synapse.
  • These findings suggest a potential host-protective role for Tregs in limiting viral spread during the early stages of HIV infection.

Keywords:
CTLA-4HIV-1actin cytoskeletoncyclic AMPdendritic cellsregulatory T cells

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