Measles Immune Suppression: Lessons from the Macaque Model

Measles remains a significant childhood disease,and is associated with a transient immune suppression. paradoxically,measles virus (mv) infection also induces robust mv-specific immune responses. current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells,caused by infection with or exposure to mv. we have generated stable recombinant mvs that express enhanced green fluorescent protein,and remain virulent in non-human primates. by performing a comprehensive study of virological,immunological,hematological and histopathological observations made in animals euthanized at different time points after mv infection,we developed a model explaining measles immune suppression which fits with the measles paradox. here we show that mv preferentially infects cd45ra- memory t-lymphocytes and follicular b-lymphocytes,resulting in high infection levels in these populations. after the peak of viremia mv-infected lymphocytes were cleared within days,followed by immune activation and lymph node enlargement. during this period tuberculin-specific t-lymphocyte responses disappeared,whilst strong mv-specific t-lymphocyte responses emerged. histopathological analysis of lymphoid tissues showed lymphocyte depletion in the b- and t-cell areas in the absence of apoptotic cells,paralleled by infiltration of t-lymphocytes into b-cell follicles and reappearance of proliferating cells. our findings indicate an immune-mediated clearance of mv-infected cd45ra- memory t-lymphocytes and follicular b-lymphocytes,which causes temporary immunological amnesia. the rapid oligoclonal expansion of mv-specific lymphocytes and bystander cells masks this depletion,explaining the short duration of measles lymphopenia yet long duration of immune suppression. © 2012 de vries et al.