T-cell-mediated clearance of mouse hepatitis virus strain JHM from the central nervous system

Abstract

Clearance of the neurotropic JHM strain of mouse hepatitis virus from the central nervous system was examined by the transfer of spleen cells from immunized donors. A T cell with the surface phenotype of Thy1.2+ CD4+ CD8- asialo-GM1+ Mac-1- was found to be necessary for viral clearance. The surface phenotype and adherence to nylon wool suggest that these cells are activated helper-inducer T cells. Adoptive transfer to congenic histocompatibility strains demonstrated the necessity for compatibility at the D locus of the major histocompatibility complex. The expression of the CD4 surface marker and the requirement for major histocompatibility complex class I were further studied by the transfer of cells to recipients treated with anti-CD4 or anti-CD8 monoclonal antibodies. Treatment of recipients with either the anti-CD8 or the anti-CD4 antibodies inhibited virus clearance from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system. This suggests that the CD4+ cell acts as a helper and that virus is cleared from the central nervous system by CD8+ cells that recognize viral antigen in the context of the H-2Db gene product.

Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus

“…Further, the clearance of virus requires compatibility between donor and recipient at the major histocompatibility complex (MHC) Class 1 genes. These data also indicated that a CD4+ helperT cell is required for the activation of the CD8+ effecters (Sussman et al, 1989). This dependence on CD4+ T cells has been confirmed by the in viva depletion of CD4+ and CD8' T cells (Williamson and Stohlman, 1990).…”

“…CytotoxicT lymphocytes (CTL) are an important component of the immune response to many viral infections. CTL have been implicated in the pathogenesis of MHV infection by the demonstration that a reduction in JHMV titer during infection of C57Bl/6 mice requires a CD8+ T cell (Sussman et al, 1987(Sussman et al, , 1989. Further, the clearance of virus requires compatibility between donor and recipient at the major histocompatibility complex (MHC) Class 1 genes.…”

Regulation of t cell responses during central nervous system viral infection

“…Following the inoculation of the JHM strain of mouse hepatitis virus (JHMV) into susceptible mice, for example, an acute encephalomyelitis is elicited with robust infection of astrocytes, oligodendrocytes, and, to a lesser degree, neurons. Using an adoptive transfer strategy, viral clearance from the brains of these hosts has been shown to be mediated by an H2-D-restricted, virus-specific CD8 ÷ T cell population (Sussman et al, 1989). Interestingly, these CD8 ÷ CTLs have an absolute requirement for CD4+ T cells that appear to support their local survival within the brain (Stohlman et al, 1998).…”

Mouse hepatitis virus A59 increases steady-state levels of MHC mRNAs in primary glial cell cultures and in the murine central nervous system

“…Weiss in JHM-infected mice and that CD8 + , major histocompatibility complex (MHC) class I-restricted T cells are important in viral clearance . [6][7][8][9] In addition, MHC class (restricted T cells, possibly suppressor/cytotoxic T cells (CTL), have been isolated from mice infected with JHM . 10, "…”