Characterization of T cells that are activated after depletion of major encephalitogenic T cells in rat autoimmune encephalomyelitis.
In rat experimental autoimmune encephalomyelitis (EAE), encephalitogenic T cells mainly use Vbeta8.2 of TCR, but it is not clear whether Vbeta8.2 is the sole encephalitogenic TCR. To address this issue, we examined the immunological status of Lewis rats that had been treated with anti-Vbeta8.2 mAb and immunized with myelin basic protein (MBP). It was demonstrated that rats in which the majority of Vbeta8.2+ T cells had been depleted developed clinical EAE and possessed newly expanded Vbeta10. Analysis of T cell lines established from these animals revealed that T line cells responded to a minor epitope in the MBP molecule. However, treatment with a mixture of anti-Vbeta8.2 and anti-Vbeta10 mAbs reduced the clinical severity of EAE but did not induce complete suppression of the disease due to new activation of Vbeta6. These findings suggest that rapid and frequent examination of the TCR repertoire is essential to identify pathogenic TCRs and to establish TCR-based immunotherapy for autoimmune diseases.
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183-8526, Japan. matyoh@tmin.ac.jp
Y
Y
Matsumoto
Y
Y
Jee
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000276:immunology; D016130:Immunophenotyping; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology; D043025:Oligoclonal Bands; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D004676:Myelin Basic Protein; D043025:Oligoclonal Bands; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; C079716:myelin basic protein 68-88