Comparative analysis of host responses related to immunosuppression between measles patients and vaccine recipients with live attenuated measles vaccines.

Abstract

Measles virus infection induces a profound immunosuppression. We analyzed in a time-dependent manner peripheral bloods of one to two-year-old children immunized with live attenuated measles vaccines, compared with age-matched measles patients, for immunosuppression. In contrast to transient severe lymphopenia with measles patients, primarily due to extensive apoptosis of a broad spectrum of uninfected lymphocytes, neither apoptosis nor lymphopenia occurred with measles vaccine recipients. Increase in number and activation of NK cells, which might compensate for the lymphopenia in measles patients, were not found with the vaccinees. While cell surface expression of apoptosis-related molecules such as TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-receptors, CD95(Fas) and Fas-ligand, and plasma interferon-gamma were increased for measles patients, they remained unchanged after vaccination. Plasma interleukin (IL)-18, which is responsible for inducing apoptosis in several infectious diseases, was increased predominantly with measles patients, whereas the increase remained marginal with the vaccinees. IL-10 was elevated transiently in both measles patients and vaccinees. Decrease in plasma IL-12, which is often correlated with T cell suppression, was not found for both cases. Serum IgM and IgG antibodies to measles virus were induced at lower titers in the vaccinees than measles patients. These results indicate that in contrast to wild-type measles virus, live measles vaccines hardly provoked host cytokine responses that lead to apoptotic cytolysis of uninfected lymphocytes, lymphopenia and immunosuppression, and thereby induced weaker immune responses to the virus.