The immune response in viral encephalitis

Abstract

The central nervous system (CNS) offers a unique organ system in which to study viral immunopathogenesis. The presence of the blood-brain barrier that restricts entry of cells and protein, the restricted expression of MHC antigens and the nonrenewable nature of the neuronal cell population offer challenges to the immune system for viral clearance and increase the chances for viral persistence. We have used Sindbis virus encephalitis in mice as a model system for the study of the development of immune reactions in the CNS and clearance of virus from neurons. The immune response to this and other viral infections of the CNS probably are initiated in peripheral lymphoid tissue followed by entry of activated T cells into the cerebrospinal fluid, meninges, and brain parenchyma. During Sindbis virus infection class I and II MHC antigens are expressed extensively on microglia which may present viral antigen produced by the infected neurons. Full development of the inflammatory response requires virus-specific T cells, but participating cells include NK cells, gamma delta T cells, monocytes and B cells. The entry of Ig-secreting B cells corresponds with the appearance of increased amounts of IgG and IgA in the cerebrospinal fluid. Clearance of Sindbis virus from the brain was studied using persistently infected severe combined immunodeficient (scid) mice. Passive transfer of immune serum or immune T cells to these infected mice demonstrated that antibody to a surface glycoprotein of the virus eliminated virus by a noncomplemented-mediated, noncytolytic mechanism. Immune T cells had no effect on virus replication.(ABSTRACT TRUNCATED AT 250 WORDS)