Effective and selective immune surveillance of the brain by MHC class I-restricted cytotoxic T lymphocytes.
Cytotoxic CD8(+) T cells are abundantly present in human virus-induced or putative autoimmune diseases of the central nervous system (CNS). Their direct role in the induction of inflammatory brain damage is, however, poorly understood. We have studied CD8(+) T cell-mediated brain inflammation by transferring MHC class I-restricted hemagglutinin (HA)-reactive T cells from a TCR transgenic mouse line into transgenic mice, which express HA in astrocytes. We show that activated CD8(+) T cells alone can induce monophasic brain inflammation in immunocompetent recipient animals. Similar to previous studies, involving transfer of CD4(+) cells, brain inflammation peaks after 5-7 days and then declines. The pathology of brain inflammation, however, differs fundamentally from that induced by CD4(+) cells. The inflammatory reaction is dominated by T cells and activated microglia in the virtual absence of hematogenous macrophages. This is associated with exquisitely specific destruction of antigen-containing astrocytes in the absence of any bystander damage of myelin, oligodendrocytes or neurons. Furthermore, in contrast to CD4(+) T cells, some CD8(+) cells accumulate in the brain and activate microglia in recipient animals, even in the absence of the specific antigen in the CNS. These data indicate that CD8(+) T cells are prime candidates for immune surveillance of the CNS.
INSERM U546 and Immunology Laboratory, Pitie-Salpetriere Hospital, Paris, France.
Julie
J
Cabarrocas
Jan
J
Bauer
Eliane
E
Piaggio
Roland
R
Liblau
Hans
H
Lassmann
D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology; D004660:Encephalitis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins