Memory CD4+ T-cell-mediated protection from lethal coronavirus encephalomyelitis.
The antiviral role of CD4(+) T cells in virus-induced pathologies of the central nervous system (CNS) has not been explored extensively. Control of neurotropic mouse hepatitis virus (JHMV) requires the collaboration of CD4(+) and CD8(+) T cells, with CD8(+) T cells providing direct perforin and gamma interferon (IFN-gamma)-mediated antiviral activity. To distinguish bystander from direct antiviral contributions of CD4(+) T cells in virus clearance and pathology, memory CD4(+) T cells purified from wild type (wt), perforin-deficient (PKO), and IFN-gamma-deficient (GKO) immune donors were transferred to immunodeficient SCID mice prior to CNS challenge. All three donor CD4(+) T-cell populations controlled CNS virus replication at 8 days postinfection, indicating IFN-gamma- and perforin-independent antiviral function. Recipients of GKO CD4(+) T cells succumbed more rapidly to fatal disease than untreated control infected mice. In contrast, wt and PKO donor CD4(+) T cells cleared infectious virus to undetectable levels and protected from fatal disease. Recipients of all CD4(+) T-cell populations exhibited demyelination. However, it was more severe in wt CD4(+) T-cell recipients. These data support a role of CD4(+) T cells in virus clearance and demyelination. Despite substantial IFN-gamma-independent antiviral activity, IFN-gamma was crucial in providing protection from death. IFN-gamma reduced neutrophil accumulation and directed macrophages to white matter but did not ameliorate myelin loss.
Savarin
Carine
C
Department of Neurosciences, NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Bergmann
Cornelia C
CC
Hinton
David R
DR
Ransohoff
Richard M
RM
Stohlman
Stephen A
SA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017934:Coronavirus / Q000276:immunology*; D004679:Encephalomyelitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism
D007371:Interferon-gamma