Mechanisms of killing of measles virus-infected cells by human lymphocytes: Interferon associated and unassociated cell-mediated cytotoxicity

Abstract

Human fibroblasts infected with measles virus express viral hemagglutinin (HA) and fusion (F) glycoproteins on their surface. These infected cells are killed by peripheral blood lymphocytes (PBLs) within 2 to 4 hr of incubation in vitro. Both syngeneic and allogeneic PBLs harvested from human adults, all previously recovered from childhood measles virus infection (immune donors), are efficient in mediating this cytotoxicity. Cytotoxicity is also expressed by PBLs from a donor with no history of measles virus and lacking circulating anti-measles virus antibodies. This cell-mediated cytotoxicity (CMC) is not due to anti-measles virus IgG in that it is not abrogated by purified F(ab′) 2 fragments from rabbit IgG anti-human F(ab′) 2. The killer lymphocytes are Fc-receptor positive and erythrocyte rosetting and non-erythrocyte resetting, as assessed by both positive and negative selection experiments. Exposure of viral glycoproteins at surfaces of infected cells is necessary for this early CMC, which can be completely abrogated by F(ab′) 2 fragments to measles virus glycoproteins. However, the same F(ab′) 2 fragments are not effective in blocking CMC after an 8-hr incubation period (late CMC), suggesting that a different mechanism of CMC operates at the later time. Interferon (IFN)-like activity cannot be demonstrated in culture fluids within 4 hr of incubation, and early CMC is not inhibited by antibody to human IFN. In contrast, after 8 hr of incubation, culture fluids do possess antiviral activity, and do have the capacity to recruit new CMC indicating that IFN is now present in the system. Therefore, viral glycoproteins expressed at the surface of infected cells induced CMC early in the infectious cycle and this CMC is not associated with IFN-like activity. Later during the infection, a different IFN-associated CMC is also present.