T-Cells Underlie Some but Not All of the Cerebellar Pathology in a Neonatal Rat Model of Congenital Lymphocytic Choriomeningitis Virus Infection.
Lymphocytic choriomeningitis virus (LCMV) infection during pregnancy injures the human fetal brain. Neonatal rats inoculated with LCMV are an excellent model of congenital LCMV infection because they develop cerebellar injuries similar to those in humans. To evaluate the role of T-lymphocytes in LCMV-induced cerebellar pathology, congenitally athymic rats, deficient in T-lymphocytes were compared with euthymic rats. Peak viral titers and cellular targets of infection were similar, but viral clearance from astrocytes was impaired in the athymic rats. Cytokines and chemokines rose to higher levels and for a greater duration in the euthymic rats than in their athymic counterparts. The euthymic rats developed an intense lymphocytic infiltration, accompanied by destructive lesions of the cerebellum and a neuronal migration defect because of T-cell-mediated alteration of Bergmann glia. These pathologic changes were absent in the athymic rats but were restored by adoptive transfer of lymphocytes. Athymic rats were not free of pathologic effects, however, as the virus induced cerebellar hypoplasia. Thus, T-lymphocytes play key roles in LCMV clearance, cytokine/chemokine responses, and pathogenesis of destructive lesions and neuronal migration disturbances but not all pathology is T-lymphocyte-dependent. Cerebellar hypoplasia from LCMV occurs even in the absence of T-lymphocytes and is likely due to the viral infection itself.
From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB).
Hannah
H
Klein
From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB).
Glenda K
GK
Rabe
From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB).
Bahri
B
Karacay
From the Department of Neurology (HK, DJB); Department of Pediatrics (GKR, BK); and Neuroscience Graduate Program, University of Iowa College of Medicine, Iowa City, Iowa (HK, DJB).
Daniel J
DJ
Bonthius
Bergmann glia; Encephalomalacia; Hypoplasia; Lymphocytic choriomeningitis virus (LCMV); Neuronal migration.