Lack of evidence for a pathogenic role of T-lymphocytes in an animal model for Charcot-Marie-Tooth disease 1A.
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.
Kohl
Bianca
B
Department of Neurology, Section of Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Strasse 11, D-97080 Wuerzburg, Germany.
Groh
Janos
J
Wessig
Carsten
C
Wiendl
Heinz
H
Kroner
Antje
A
Martini
Rudolf
R
D000818:Animals; D001369:Axons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D009185:Myelin Proteins; C073687:PMP22 protein, human