Immune cells perturb axons and impair neuronal survival in a mouse model of infantile neuronal ceroid lipofuscinosis

Janos Groh, Thomas G. Kühl, Chi Wang Ip, Hemanth R. Nelvagal, Sarmi Sri, Steven Duckett, Myriam Mirza, Thomas Langmann, Jonathan D. Cooper, Rudolf Martini

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


The neuronal ceroid lipofuscinoses are fatal neurodegenerative disorders in which the visual system is affected early in disease progression. A typical accompanying feature is neuroinflammation, the pathogenic impact of which is presently obscure. Here we investigated the role of inflammatory cells in palmitoyl protein thioesterase 1-deficient (Ppt1-/-) mice, a model of infantile neuronal ceroid lipofuscinosis (CLN1 disease, infantile), predominantly focusing on the visual system. We detected an early infiltration of CD8+ T-lymphocytes and observed activation of microglia/macrophage-like cells. To analyse the pathogenic impact of lymphocytes, we crossbred Ppt1 -/- mice with mutants lacking lymphocytes (Rag1-/-), and scored axonal transport, axonal perturbation and neuronal survival. This lack of lymphocytes led to a significant amelioration of disease phenotypes, not only in the retino-tectal system, but also in other regions of the central nervous system. Finally, reconstitution experiments revealed a crucial role of CD8+ T-lymphocytes in pathogenesis. Our study provides novel pathomechanistic insights that may be crucial for developing treatment strategies.

Original languageEnglish
Pages (from-to)1083-1101
Number of pages19
Issue number4
StatePublished - Apr 2013


  • T-lymphocytes
  • axonal damage
  • neurodegeneration
  • neuroinflammation
  • neuronal ceroid lipofuscinosis


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