Summary auto-generated
This study investigates the mechanism by which measles virus (MV) causes immunosuppression in vitro. The researchers examined how UV-inactivated MV-infected cells can suppress the proliferation of uninfected lymphocytes in coculture. Using human peripheral blood lymphocytes (PBLs) and Jurkat T cell clones, they found that contact between MV-infected presenter cells and uninfected responder cells dramatically inhibited mitogen-induced proliferation. Importantly, this inhibition occurred independently of apoptosis, as cells with differing susceptibilities to CD95-mediated apoptosis were equally suppressed. The researchers observed that responder cells maintained normal expression of activation markers including IL-2 receptor components and other T cell markers, indicating viable cell activation. Although IL-2 release was reduced after MV contact, exogenous IL-2 supplementation could not restore proliferation. Cell cycle analysis revealed that a significantly higher fraction of responder cells accumulated in the G0/G1 phase following MV contact compared to controls. These findings demonstrate that MV-induced immunosuppression operates through cell cycle arrest rather than programmed cell death.
Key findings
- MV-induced immunosuppression does not involve apoptosis—cells resistant to CD95-mediated apoptosis are equally sensitive to MV-contact-mediated inhibition
- Responder cells maintain viable, activated phenotypes with normal expression of IL-2 receptor components and activation markers despite proliferative arrest
- Reduced IL-2 release does not account for growth inhibition, as exogenous IL-2 addition fails to restore proliferation
- MV-contact induces accumulation of responder cells in the G0/G1 phase of the cell cycle (82-83% vs 69-72% in controls)
- Proliferative inhibition is mediated by direct contact between MV-infected cells and uninfected cells expressing MV glycoproteins F and H
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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.