Measles Immune Suppression: Lessons from the Macaque Model

PLoS Pathogens

W. Paul Duprex¹  Stephen McQuaid²  Albert D. M. E. Osterhaus³  Geert van Amerongen³  Selma Yüksel³  R. Joyce Verburgh³  Rik L. de Swart³  Rory D. de Vries³ 

[1] Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America;Tissue Pathology, Belfast Health and Social Care Trust, Queen's University of Belfast, Belfast, Northern Ireland, United Kingdom;Viroscience Lab, Erasmus MC, Rotterdam, The Netherlands

关键词: Macaque;    T cells;    Lymphocytes;    Immune suppression;    Measles virus;    B cells;    Opportunistic infections;    Measles;   

DOI  :  10.1371/journal.ppat.1002885

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY