engleski

CD8+ T Lymphocyte Mediated Immune Response in MCMV-Infected Newborn Brain

Congenital human cytomegalovirus (HCMV) infection may result in wide spread encephalitis and developmental abnormalities of newborn brain. In order to study the pathogenesis of HCMV infection in developing central nervous system (CNS) we have established a model of peripheral MCMV infection of newborn mice. MCMV readily spread into the CNS following intraperitoneal infection, leading to the development of meningoencephalitis. Productive infection in the brain was visible starting from day 7 post infection (p.i.), and lasting until day 21 p.i. Congruent with the virus clearance T lymphocyte infiltration in the CNS was observed. CD8+ T cells presented the predominant immune population in infected brain. Although CD8+ T cells have been shown to be critical for the viral clearance from peripheral organs in adult mice, quantitative and qualitative differences between neonatal and adult immune responses raised the possibility that these cells could not effectively control the infection in newborn brain. CNS-infiltrating CD8+ T cells presented an effector phenotype by expressing the high level of CD44 and CD69 molecules on their cell surface. Antiviral specificity of accumulating CD8+ T cells was established by staining with tetramers loaded with different MCMV epitopes. This virus specific CD8+ T cells stimulated ex vivo with IE1 encoded peptide secreted IFNγ . CD8+ T cell depletion was fatal for infected newborn mice by day 15 p.i., while adoptive transfer of CNS isolated CD8+ T cells into adult immunodepleted infected mice resulted in lower viral burden in peripheral organs of these mice. These results show that functionally mature CD8+ T cells infiltrate the MCMV-infected newborn brain and have an important role in the control of the virus replication and clearance from the developing CNS.

MCMV CD8 brain newborn

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