Document Detail

CD8+ T lymphocytes control murine cytomegalovirus replication in the central nervous system of newborn animals.
MedLine Citation:
PMID:  18641350     Owner:  NLM     Status:  MEDLINE    
Human CMV infection of the neonatal CNS results in long-term neurologic sequelae. To define the pathogenesis of fetal human CMV CNS infections, we investigated mechanisms of virus clearance from the CNS of neonatal BALB/c mice infected with murine CMV (MCMV). Virus titers peaked in the CNS between postnatal days 10-14 and infectious virus was undetectable by postnatal day 21. Congruent with virus clearance was the recruitment of CD8(+) T cells into the CNS. Depletion of CD8(+) T cells resulted in death by postnatal day 15 in MCMV-infected animals and increased viral loads in the liver, spleen, and the CNS, suggesting an important role for these cells in the control of MCMV replication in the newborn brain. Examination of brain mononuclear cells revealed that CD8(+) T cell infiltrates expressed high levels of CD69, CD44, and CD49d. IE1(168)-specific CD8(+) T cells accumulated in the CNS and produced IFN-gamma and TNF-alpha but not IL-2 following peptide stimulation. Moreover, adoptive transfer of brain mononuclear cells resulted in decreased virus burden in immunodepleted MCMV-infected syngeneic mice. Depletion of the CD8(+) cell population following transfer eliminated control of virus replication. In summary, these results show that functionally mature virus-specific CD8(+) T cells are recruited to the CNS in mice infected with MCMV as neonates.
Glenn R B Bantug; Djurdijca Cekinovic; Russell Bradford; Thad Koontz; Stipan Jonjic; William J Britt
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-21     Completed Date:  2008-08-19     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2111-23     Citation Subset:  AIM; IM    
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MeSH Terms
Aging / physiology
Animals, Newborn
Brain / immunology,  virology
CD8-Positive T-Lymphocytes / cytology,  immunology*,  metabolism
Cell Movement / immunology
Cell Separation
Cells, Cultured
Central Nervous System Diseases / immunology*,  metabolism,  pathology,  virology*
Herpesviridae Infections / immunology,  pathology,  virology
Immediate-Early Proteins / immunology
Interferon-gamma / biosynthesis,  immunology
Liver / immunology
Mice, Inbred BALB C
Monocytes / cytology,  immunology
Muromegalovirus / physiology*
Survival Rate
Virus Replication*
Grant Support
Reg. No./Substance:
0/IE1 protein, cytomegalovirus; 0/Immediate-Early Proteins; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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