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CD3ε Expression Defines Functionally Distinct Subsets of Vδ1 T Cells in Patients With Human Immunodeficiency Virus

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  • 1Discipline of Immunology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.

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In human immunodeficiency virus (HIV) infection, Vδ1 T cells increase but often show exhaustion. A subset of these cells, CD3εhi Vδ1 T cells, produce IL-17, while CD3εlo cells are terminally differentiated.

Keywords:
CD3εVδ1 T cellsflow cytometryhuman immunodeficiency virusinterleukin-17programmed death-1

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Human γδ T cells, specifically Vδ1 T cells, recognize antigens without MHC restriction and produce IL-17.
  • Vδ1 T cells are known to expand in individuals with human immunodeficiency virus (HIV) infection.

Purpose of the Study:

  • To investigate the characteristics and function of Vδ1 T cells in HIV infection.
  • To identify distinct subsets of Vδ1 T cells and their roles in IL-17 production and T cell exhaustion.

Main Methods:

  • Flow cytometry and confocal microscopy were used to analyze Vδ1 T cell populations.
  • Vδ1 T cell lines from healthy donors were cultured with IL-2 to study CD3ε expression dynamics.
  • In vitro stimulation was performed to assess IL-17 production by different Vδ1 T cell subsets.

Main Results:

  • Patients with HIV exhibit elevated frequencies of circulating Vδ1 T cells, particularly with *Candida albicans* co-infection.
  • Two Vδ1 T cell populations were identified: CD3εlo and CD3εhi, based on CD3ε chain expression.
  • CD3εlo Vδ1 T cells showed terminally differentiated phenotypes and expressed PD-1, indicating exhaustion.
  • Only the CD3εhi Vδ1 T cell subset produced IL-17 upon stimulation, while CD3εlo cells did not.

Conclusions:

  • Vδ1 T cells represent an alternative source of IL-17 in the context of HIV infection, compensating for CD4+ T cell depletion.
  • A significant proportion of Vδ1 T cells in HIV patients display features of exhaustion, mediated by PD-1 expression or CD3ε downregulation.
  • Understanding these Vδ1 T cell subsets is crucial for developing immune-based therapies for HIV.