title: Cell cycle arrest rather than apoptosis is associated with measles virus contact-mediated immunosuppression in vitro.
abstract: Acute measles is associated with pronounced immunosuppression characterized both by leukopenia and impaired lymphocyte functions. In an earlier study, we found that mitogen-dependent proliferation of uninfected human peripheral blood lymphocytes (PBLs) and spontaneous proliferation of human cell lines of lymphocytic or monocytic origin was impaired after contact with UV-inactivated, measles virus (MV)-infected cells, UV-inactivated MV or with cells transfected with MV glycoproteins (gp) F and H. We now show that mitogen-stimulated PBLs and Jurkat cell clones either highly sensitive or resistant to CD95-induced apoptosis have a similar sensitivity to MV-induced inhibition and do not undergo apoptosis. Moreover, unimpaired mitogen-dependent upregulation of important activation markers, including IL-2R, was observed in PBL cultures after contact with MV-infected, UV-irradiated presenter cells. This indicates that the cells were indeed viable and acquire a state of activation. Less IL-2 was released from PBLs after contact with MV-infected presenter cells when compared with that released after contact with uninfected cells. However, mitogen-induced proliferation of PBLs was not restored by addition of IL-2 under these conditions. It appeared that a higher fraction of mitogen-stimulated PBLs accumulated in the G0/G1 phase of the cell cycle after contact with MV-infected cells. Thus, the mitogen-unresponsiveness of PBLs seen after contact with MV-infected cells is due to cell cycle arrest rather than apoptosis.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Germany.
authors.forename: J J
authors.initials: JJ
authors.lastname: Schnorr
authors.forename: M
authors.initials: M
authors.lastname: Seufert
authors.forename: J
authors.initials: J
authors.lastname: Schlender
authors.forename: J
authors.initials: J
authors.lastname: Borst
authors.forename: I C
authors.initials: IC
authors.lastname: Johnston
authors.forename: V
authors.initials: V
authors.lastname: ter Meulen
authors.forename: S
authors.initials: S
authors.lastname: Schneider-Schaulies
mesh_terms: D000328:Adult; D017209:Apoptosis; D002453:Cell Cycle; D006801:Humans; D007165:Immunosuppression Therapy; D019169:Jurkat Cells; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D008459:Measles virus / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*