T-cell heterogeneity in muscle lesions of inclusion body myositis.
In the muscle lesions of inclusion body myositis (IBM), two populations of T cells can morphologically be distinguished, T cells that invade muscle fibers and T cells that remain in interstitial areas. Using combined immunohistochemistry and RT-PCR, we analysed the TCR expressed by these distinct T cell populations. In three of eight IBM muscle specimens, the autoinvasive T cells were stained with one of the available mAbs: anti-Vbeta5.3 in patient 1, anti-Vbeta5.2 in patient 2, and anti-Vbeta3 in patient 3. The corresponding TCR Vbeta mRNAs were amplified by RT-PCR and the PCR products were cloned and sequenced. In all three specimens, the TCRs expressed by the autoinvasive T cells were clonally restricted. Furthermore, in patient 1 two different mAbs labelled two distinct populations of T cells: an autoaggressive population of CD8 + Vbeta5.3 + cells that invaded muscle fibers and a noninvasive interstitial population of CD8 - Vbeta5.1 + cells. TCR sequence analysis revealed that the noninvasive Vbeta5.1 + T cells were clonally diverse, whereas the autoinvasive Vbeta5.3 + T cells were clonally restricted.
Bender
A
A
Department of Neuroimmunology, Max Planck Institute, Martinsried, Germany.
Behrens
L
L
Engel
A G
AG
Hohlfeld
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D019674:Genes, T-Cell Receptor beta / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009132:Muscles / Q000502:physiology; D018979:Myositis, Inclusion Body / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell