CELL-CYCLE ARREST RATHER THAN APOPTOSIS IS ASSOCIATED WITH MEASLES-VIRUS CONTACT-MEDIATED IMMUNOSUPPRESSION IN-VITRO

Acute measles is associated with pronounced immunosuppression characte rized both by leukopenia and impaired lymphocyte functions. In an earl ier study, we found that mitogen-dependent proliferation of uninfected human peripheral blood lymphocytes (PBLs) and spontaneous proliferati on 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 cl ones either highly sensitive or resistant to CD95-induced apoptosis ha ve a similar sensitivity to MV-induced inhibition and do not undergo a poptosis, Moreover, unimpaired mitogen-dependent upregulation of impor tant activation markers, including IL-2R, was observed in PBL cultures after contact with MV-infected, UV-irradiated presenter cells, This i ndicates that the cells were indeed viable and acquire a state of acti vation, Less IL-2 was released from PBLs after contact with MV-infecte d presenter cells when compared with that released after contact with uninfected cells, However, mitogen-induced proliferation of PBLs was n ot restored by addition of IL-2 under these conditions, It appeared th at 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-infec ted cells is due to cell cycle arrest rather than apoptosis.