Mouse hepatitis virus-specific cytotoxic T lymphocytes protect from lethal infection without eliminating virus from the central nervous system

Abstract

Acute infection of the central nervous system by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces nucleocapsid protein specific cytotoxic T lymphocytes (CTL) not found in the periphery (S. Stohlman, S. Kyuwa, J. Polo, D. Brady, M. Lai, and C. Bergmann, J. Virol. 67:7050-7059, 1993). Peripheral induction of CTL specific for the nucleocapsid protein of JHMV by vaccination with recombinant vaccinia viruses was unable to provide significant protection to a subsequent lethal virus challenge. By contrast, the transfer of nucleoprotein-specific CTL protected mice from a subsequent lethal challenge by reducing virus replication within the central nervous system, demonstrating the importance of the CTL response to this epitope in JHMV infection. Transfer of these CTL directly into the central nervous system was at least 10-fold more effective than peripheral transfer. Histological analysis indicated that the CTL reduced virus replication in ependymal cells, astrocytes, and microglia. Although the CTL were relatively ineffective at reducing virus replication in oligodendroglia, survivors showed minimal evidence of virus persistence within the central nervous system and no evidence of chronic ongoing demyelination.

Adoptive Transfer of Infectious Bronchitis Virus Primed αβ T Cells Bearing CD8 Antigen Protects Chicks from Acute Infection

“…In evaluating the role of T lymphocytes in murine hepatitis virus (MHV) infection in the central nervous system, the adoptive transfer of both a CD8 ϩ T cell clone and a CD4 ϩ T cell clone was shown to suppress viral growth and viral antigen-positive cells in the brain (Yamaguchi et al, 1988). In addition, the transfer of MHV nucleoprotein-specific CTL protected mice from a subsequent lethal MHV challenge by reducing virus replication within the central nervous system (Stohlman et al, 1995). Transfer of these CTL directly into the central nervous system was at least 10-fold more effective than peripheral transfer.…”

Activated GL7+ B cells are maintained within the inflamed CNS in the absence of follicle formation during viral encephalomyelitis

“…By day 14 p. i., GL7 + cells formed well-demarcated structures typical of GCs, but were also loosely scattered within follicles as well as at the T cell/ B cell border. Mature GCs, characterized by distinct light and dark zones, were not evident until day 21 p.i., when infectious virus has already been cleared from the CNS (Phares et al, 2016;Stohlman et al, 1995). GL7 expression was also monitored by flow cytometry to quantify the relative expression as well as the proportion of GC phenotype B cells over time.…”

Regulation of t cell responses during central nervous system viral infection

“…The adoptive transfer of primed T cells can protect naive mice from a variety of otherwise lethal viral infections (Zinkernagel and Welsh, 1976;Yap et al, 1978;Jacoby et al, 1980;Sethi et al, 1983;Stohlman et al, 1986;Stohlman et al, 1995). In some situations, transferred T cells play an active role in suppressing virus replication, serving as the primary means through which they protect their hosts.…”