Measles is a highly contagious childhood disease associated with an immunological paradox: although a strong virus-specific immune response results in virus clearance and the establishment of a life-long immunity,
measles infection is followed by an acute and profound immunosuppression leading to an increased susceptibility to
secondary infections and high infant mortality. In certain cases,
measles is followed by fatal neurological complications. To elucidate
measles immunopathology, we have analyzed the immune response to measles virus in mice transgenic for the
measles virus receptor, human CD150. These animals are highly susceptible to intranasal
infection with wild-type
measles strains. Similarly to what has been observed in children with
measles,
infection of suckling transgenic mice leads to a robust activation of both T and B lymphocytes, generation of virus-specific cytotoxic T cells and antibody responses. Interestingly, Foxp3(+)CD25(+)CD4(+) regulatory T cells are highly enriched following
infection, both in the periphery and in the brain, where the virus intensively replicates. Although specific anti-viral responses develop in spite of increased frequency of regulatory T cells, the capability of T lymphocytes to respond to virus-unrelated
antigens was strongly suppressed. Infected adult CD150 transgenic mice crossed in an
interferon receptor type I-deficient background develop generalized immunosuppression with an increased frequency of CD4(+)CD25(+)Foxp3(+) T cells and strong reduction of the
hypersensitivity response. These results show that measles virus affects regulatory T-cell homeostasis and suggest that an interplay between virus-specific effector responses and regulatory T cells plays an important role in
measles immunopathogenesis. A better understanding of the balance between
measles-induced effector and regulatory T cells, both in the periphery and in the brain, may be of critical importance in the design of novel approaches for the prevention and treatment of
measles pathology.