Suppression of R5-type of HIV-1 in CD4+ NKT cells by Vδ1+ T cells activated by flavonoid glycosides, hesperidin and linarin.
Michiyuki YonekawaMasumi ShimizuAtsushi KanekoJiro MatsumuraHidemi TakahashiPublished in: Scientific reports (2019)
We established transfectants expressing T cell receptors (TCRs) either for Vγ1 and Vδ1 (1C116) or for Vγ2 and Vδ2 (2C21) using the TCR-deficient Jurkat T cell line J.RT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. Clone 2C21 was specifically stimulated by previously reported ligands for Vγ2Vδ2 (Vδ2)-TCR such as isopentenyl pyrophospate (IPP), ethylamine, or risedronate. In contrast, clone 1C116 was strongly stimulated through the Vγ1Vδ1 (Vδ1)-TCR by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring. Additionally, hesperidin and linarin showed stimulatory activity for peripheral blood mononuclear cell (PBMC)-derived T cells expressing Vδ1-TCR; these activated Vδ1+ T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. Such PBMC-derived Vδ1+ T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in CD4+ NKT cells in a dose-dependent manner. To the best of our knowledge, this is the first demonstration that flavonoid glycosides activate functional Vδ1+ T cells.
Keyphrases
- regulatory t cells
- peripheral blood
- induced apoptosis
- antiretroviral therapy
- cell cycle arrest
- hiv positive
- hiv infected
- human immunodeficiency virus
- hepatitis c virus
- hiv testing
- hiv aids
- dendritic cells
- healthcare
- sars cov
- endoplasmic reticulum stress
- single cell
- south africa
- stem cells
- magnetic resonance imaging
- signaling pathway
- cell proliferation
- cell death
- immune response
- mesenchymal stem cells
- pi k akt
- bone marrow