title: CTL effector function within the central nervous system requires CD4+ T cells.
abstract: CTL responses induced during most viral infections are independent of help derived from the CD4+ T cell population. However, clearance of virus from the central nervous system (CNS) during infection with the neurotropic JHM strain of mouse hepatitis virus is inhibited in the absence of CD4+ T cells. Adoptive transfer of activated CD8+ T cells with virus-specific cytolytic activity into CD4+ T cell-depleted hosts demonstrated that CD4+ T cells were one component of the host response required for expression of CTL effector function(s) within the CNS. Analysis of mice infected with the JHM strain of mouse hepatitis virus demonstrated that, in contrast to CD8+ T cells, few CD4+ T cells entered the brain parenchyma. Although fewer CD8+ T cells entered the brain parenchyma in mice depleted of CD4+ T cells, access of CTL was not inhibited in the absence of CD4+ T cells. The number of apoptotic lymphocytes in the CNS increased in the absence of CD4+ T cells, suggesting that CTL enter the CNS during viral infection in a CD4-independent manner. However, these cells rapidly undergo apoptosis, indicating that expression of CTL effector function with the parenchyma of the CNS is CD4 dependent. These data raise the possibility that programmed cell death of CD8+ T cells within the CNS is due to the increased Ag present in the CNS of infected CD4 depleted mice or that autocrine cytokines, which maintain CTL activity within peripheral tissues, are inhibited in the microenvironment of the CNS.
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles 90033, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Stohlman
authors.forename: C C
authors.initials: CC
authors.lastname: Bergmann
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
authors.forename: D J
authors.initials: DJ
authors.lastname: Cua
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*