Expansion of human gamma/delta T cells in vitro is differentially regulated by the measles virus glycoproteins.
Impaired proliferative response of lymphocytes after mitogenic stimulation ex vivo is a key feature of the generalized immunosuppression induced by measles virus (MV). Compelling evidence suggests that negative signalling by the MV glycoprotein (gp) complex and the surface of uninfected lymphocytes is essential for this effect. So far, the inhibitory activity of this complex applied to all lymphocyte subpopulations irrespective of the mode of stimulation and could not be overcome by external stimulation. This study shows that the isopentenyl pyrophosphate (IPP)/IL-2-stimulated expansion of human gamma/delta T cell receptor (TCR) T cells from peripheral blood mononuclear cells (PBMCs) is inhibited efficiently when the MV gp complex is expressed on the surface of persistently MV-infected T or monocytic cells. In contrast, persistently infected B cells or infected human dendritic cells (DCs) do not interfere with expansion of gamma/delta TCR T cells from PBMCs. These particular two cell populations, however, efficiently inhibit IPP/IL-2-stimulated expansion of gamma/delta TCR T cells from purified T cells and this is reverted by resubstitution with monocytes. As revealed by filter experiments, cocultivation with B cells and DCs empower monocytes, at least partially by soluble mediators, to provide membrane contact-dependent costimulatory signals that neutralize the inhibitory effect of the MV gp complex. Thus, gamma/delta TCR T cells are sensitive to MV gp-mediated inhibition; however, this is overcome efficiently by signals delivered from monocytes conditioned by B cells and DCs.
Bieback
Karen
K
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
Breer
Claudia
C
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
Nanan
Ralph
R
Children's Hospital, University of Würzburg, Josef-Schneider-Str. 2, D-97078 Würzburg, Germany.
Meulen
Volker Ter
VT
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
Schneider-Schaulies
Sibylle
S
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany.
D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006023:Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D045782:Hemiterpenes; D006801:Humans; D007376:Interleukin-2; D008213:Lymphocyte Activation / Q000187:drug effects*; D008457:Measles / Q000821:virology; D008459:Measles virus / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000378:metabolism / Q000494:pharmacology*
D006023:Glycoproteins; D045782:Hemiterpenes; D007376:Interleukin-2; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014764:Viral Proteins; C004809:isopentenyl pyrophosphate