Brain, Vol. 122, No. 3, 523-535,
March 1999
© 1999 Oxford University Press
Article |
Heterogeneity of T-cell receptor usage in experimental autoimmune neuritis in the Lewis rat
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1 Departments of Neurology and 2 Virology and Immunobiology, Julius-Maximilians Universität, Würzburg, Germany and 3 Immunology Department/IMM3 Scripps Clinic and Research Foundation, La Jolla, California, USA
Correspondence to:
Ralf Gold, MD, Department of Neurology, University of Würzburg, Josef-Schneider-Straße 11, D-97080 Würzburg, Germany E-mail r.gold{at}mail.uni-wuerzburg.de
In experimental autoimmune neuritis (EAN), T-cell receptor (TCR) variable (V)-region gene usage by neuritogenic T cells has been reported to be clonally restricted at the RNA level. This study was designed to verify TCR usage by neuritogenic T cells at the protein level. We generated two monoclonal antibodies (mAbs) 7H4 and 8G8 specific for a Vß4/V
11 associated idiotype expressed by the majority of neuritogenic cells of P2-specific T-cell lines. The remaining neuritogenic P2-specific T cells either exhibited a dominant usage of the TCR Vß13 chain recognized by the recently generated mAbs 17D5 and 18B1 or showed diverse Vß usage. Treatment of adoptive-transfer (AT)-EAN or of EAN actively induced with the neuritogenic P2 peptide by mAbs 7H4 and 8G8 led to a partial, but significant, reduction of clinical disease. Treatment with Vß13-specific mAb 17D5 had no clear effect on active EAN. Our data show that at least three different TCR are used by P2-specific pathogenic T cells in EAN, an animal model for human inflammatory neuropathies.
GuillainBarré syndrome; EAN therapy; antibodies; T-cell receptors
AT-EAN = adoptive transfer EAN; cDNA = complementary DNA; EAE = experimental autoimmune encephalomyelitis; EAN = experimental autoimmune neuritis; FACS = fluorescence-activated cell sorter; mAb = monoclonal antibody; MBP = myelin basic protein; PCR = polymerase chain reaction; rhP2 = recombinant human P2; RTPCR = reverse transcriptionPCR; TCR = T-cell receptor; V = variable
* Present address: Department of Neurology, University of Regensburg, 93053, Regensburg, Germany
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