Lack of evidence for a pathogenic role of T-lymphocytes in an animal model for Charcot-Marie-Tooth disease 1A. Neurobiol Dis 2010 Apr;38(1):78-84
Date
01/13/2010Pubmed ID
20064611DOI
10.1016/j.nbd.2010.01.001Scopus ID
2-s2.0-77549084418 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
We have previously shown that in two distinct models for inherited neuropathies of the Charcot-Marie-Tooth (CMT) type, T-lymphocytes are critically involved in demyelination. In the present study, we tested whether T-lymphocytes have a similar pathogenetic impact in another CMT model, i.e., in mice overexpressing the peripheral myelin protein (PMP)-22, representing the most prevalent form CMT1A. By cross breeding the myelin mutant mice with mutants lacking mature T- and B-lymphocytes (RAG-1-deficient mice), the pathological alterations were not changed in comparison to PMP22 mutants with a normal immune system. Reciprocal enhancement of lymphocyte activation, by inactivation of the lymphocytic co-inhibitor programmed death-1, also did not alter pathological changes, as opposed to models with approved lymphocytic involvement. These findings strongly suggest that lymphocytes are not pathogenetically relevant in this model for CMT1A. We suggest that - in contrast to myelin phagocytosing macrophages - T-lymphocytes are not a promising target for treatment of CMT1A.
Author List
Kohl B, Groh J, Wessig C, Wiendl H, Kroner A, Martini RAuthor
Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAxons
B-Lymphocytes
Bone Marrow Transplantation
Cells, Cultured
Charcot-Marie-Tooth Disease
Disease Models, Animal
Humans
Lymphocyte Activation
Macrophages
Mice
Mice, Knockout
Mice, Transgenic
Myelin Proteins
Myelin Sheath
Peripheral Nerves
T-Lymphocytes
