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© Charles Dauguet
Virus VIH-1 (HIV-1), responsable du sida. Première étape de pénétration dans la cellule. Le virus s'approche du lymphocyte T4 et arrive à proximité de son point d'ancrage le récepteur CD4 qui reconnaît spécifiquement la protéine d'enveloppe virale gp120. On voit nettement le manteau de clathrine qui participe au processus d'endocytose (Grossissement X 190000). Image colorisée.
Publication : PloS one

Suppression by thimerosal of ex-vivo CD4+ T cell response to influenza vaccine and induction of apoptosis in primary memory T cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PloS one - 01 Apr 2014

Loison E, Poirier-Beaudouin B, Seffer V, Paoletti A, Abitbol V, Tartour E, Launay O, Gougeon ML

Link to Pubmed [PMID] – 24690681

PLoS ONE 2014;9(4):e92705

Thimerosal is a preservative used widely in vaccine formulations to prevent bacterial and fungal contamination in multidose vials of vaccine. Thimerosal was included in the multidose non-adjuvanted pandemic 2009 H1N1 vaccine Panenza. In the context of the analysis of the ex-vivo T cell responses directed against influenza vaccine, we discovered the in vitro toxicity Panenza, due to its content in thimerosal. Because thimerosal may skew the immune response to vaccines, we investigated in detail the ex-vivo effects of thimerosal on the fate and functions of T cells in response to TCR ligation. We report that ex-vivo exposure of quiescent or TCR-activated primary human T cells to thimerosal induced a dose-dependent apoptotic cell death associated with depolarization of mitochondrial membrane, generation of reactive oxygen species, cytochrome c release from the mitochondria and caspase-3 activation. Moreover, exposure to non-toxic concentrations of thimerosal induced cell cycle arrest in G0/G1 phase of TCR-activated T cells, and inhibition of the release of proinflammatory cytokines such as IFN gamma, IL-1 beta, TNF alpha, IL-2, as well as the chemokine MCP1. No shift towards Th2 or Th17 cells was detected. Overall these results underline the proapoptotic effect of thimerosal on primary human lymphocytes at concentrations 100 times less to those contained in the multidose vaccine, and they reveal the inhibitory effect of this preservative on T-cell proliferation and functions at nanomolar concentrations.

http://www.ncbi.nlm.nih.gov/pubmed/24690681