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Eur J Clin Invest. 2003 May;33(5):434-42.

Measles virus induces apoptosis in uninfected bystander T cells and leads to granzyme B and caspase activation in peripheral blood mononuclear cell cultures.

Author information

1
University of Turku, Turku, Finland. tytti.vyorinen@utu.fi

Abstract

BACKGROUND:

Measles causes lymphopenia and depresses cell-mediated immunity, but the mechanisms of immunosuppression and cell loss are poorly known.

METHODS:

We have used an in vitro model of measles virus (MV)-infected peripheral blood mononuclear cells (PBMCs) and phytohaemagglutinin-stimulated PBMCs in order to assess MV-leucocyte interactions. Cell population undergoing apoptosis was measured by flow cytometry and Annexin-V-fluos staining. The expression of Fas, FasL, TNRF1, and Bcl-2 was analyzed by flow cytometry and Western blotting, and activation of caspase cascade was measured using a colourimetric caspase substrate set. The effects of caspase inhibitors were detected by flow cytometry.

RESULTS:

Measles virus was able to infect monocytes, but interestingly induced apoptosis in uninfected T cells, indicating that induction of apoptosis in T cells is mediated by MV-infected adherent cells. Only 1% of T cells contained MV antigen day 3 p.i. Interestingly the percentage of early apoptotic T cells at the same time was 35%, showing that apoptosis was not the result of MV infection in T cells. Measles virus-induced Fas but not FasL or TNFR1 expression on PMBC, as well as activation of granzyme B and caspase cascade. Simultaneously, overexpression of Bcl-2 protein was detected. Caspase inhibitor decreased the amount of apoptotic T cells.

CONCLUSION:

Measles virus-infected monocytes induce apoptosis in uninfected T cells, suggesting that infected monocytes probably interact via cell-surface molecules with uninfected T cells and induce apoptosis by indirect mechanisms. Apoptosis of the lymphocytes may contribute to the pathogenesis of MV-induced immunosuppression and cell loss.

[Indexed for MEDLINE]

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