CMT 1A: Lack of evidence for a pathogenic role of T-lymphocytes in an animal mod

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Neurobiol Dis. 2010 Jan 8.

Lack of evidence for a pathogenic role of T-lymphocytes in an animal model for

Charcot-Marie-Tooth disease 1A.

Kohl B, Groh J, Wessig C, Wiendl H, Kroner A, i R.

Department of Neurology, Section of Developmental Neurobiology, University of

Wuerzburg, f-Schneider-Str. 11, D-97080 Wuerzburg, Germany.

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.