Measles immune suppression: lessons from the macaque model

PLoS Pathog. 2012;8(8):e1002885. doi: 10.1371/journal.ppat.1002885. Epub 2012 Aug 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / virology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Disease Models, Animal
  • Female
  • Fluorescent Dyes
  • Green Fluorescent Proteins
  • Humans
  • Immunologic Memory
  • Immunosuppression*
  • Leukocyte Common Antigens / immunology
  • Leukopenia / immunology
  • Leukopenia / virology
  • Lymphocyte Depletion
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / virology
  • Macaca
  • Male
  • Measles / immunology*
  • Measles / virology
  • Measles virus / immunology*
  • Measles virus / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology
  • Viremia / immunology
  • Viremia / virology

Substances

  • Fluorescent Dyes
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Leukocyte Common Antigens