Thymic involution, a co-morbidity factor in amyotrophic lateral sclerosis

Akop Seksenyan, Noga Ron-Harel, David Azoulay, Liora Cahalon, Michal Cardon, Patricia Rogeri, Minhee K. Ko, Miguel Weil, Shlomo Bulvik, Gideon Rechavi, Ninette Amariglio, Eli Konen, Maya Koronyo-Hamaoui, Raz Somech, Michal Schwartz

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32 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a devastating disease, characterized by extremely rapid loss of motor neurons. Our studies over the last decade have established CD4+ T cells as important players in central nervous system maintenance and repair. Those results, together with recent findings that CD4+ T cells play a protective role in mouse models of ALS, led us to the current hypothesis that in ALS, a rapid T-cell malfunction may develop in parallel to the motor neuron dysfunction. Here, we tested this hypothesis by assessing thymic function, which serves as a measure of peripheral T-cell availability, in an animal model of ALS (mSOD1 [superoxide dismutase] mice; G93A) and in human patients. We found a significant reduction in thymic progenitor-cell content, and abnormal thymic histology in 3-4-month-old mSOD1 mice. In ALS patients, we found a decline in thymic output, manifested in the reduction in blood levels of T-cell receptor rearrangement excision circles, a non-invasive measure of thymic function, and demonstrated a restricted T-cell repertoire. The morbidity of the peripheral immune cells was also manifested in the increase of pro-apoptotic BAX/BCXL2 expression ratio in peripheral blood mononuclear cells (PBMCs) of these patients. In addition, gene expression screening in the same PBMCs, revealed in the ALS patients a reduction in key genes known to be associated with T-cell activity, including: CD80, CD86, IFNG and IL18. In light of the reported beneficial role of T cells in animal models of ALS, the present observation of thymic dysfunction, both in human patients and in an animal model, might be a co-pathological factor in ALS, regardless of the disease aetiology. These findings may lead to the development of novel therapeutic approaches directed at overcoming the thymic defect and T-cell deficiency.

Original languageEnglish
Pages (from-to)2470-2482
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Issue number10
StatePublished - Oct 2010
Externally publishedYes


  • Amyotrophic lateral sclerosis
  • Immune deficiency
  • Immunomodulation
  • Neurodegeneration
  • Neuroprotection
  • Protective autoimmunity
  • T cells
  • Thymus involution


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