Successful TCR-based immunotherapy for autoimmune myocarditis with DNA vaccines after rapid identification of pathogenic TCR.
The identification of TCRs of autoimmune disease-inducing T cells within a short period of time is a key factor for designing TCR-based immunotherapy during the course of the disease. In this study, we show that experimental autoimmune carditis-associated TCRs, Vbeta8.2 and Vbeta10, were determined by complementarity-determining region 3 (CDR3)-spectratyping analysis and subsequent sequencing of the CDR3 region of spectratype-derived TCR clones. Immunotherapy targeting both Vbeta8.2 and Vbeta10 TCRs using mAbs and DNA vaccines significantly reduced the histological severity of experimental autoimmune carditis and completely suppressed the inflammation in some animals. Since depletion or suppression of one of two types of effector cells does not improve the severity of the disease significantly, combined TCR-based immunotherapy should be considered as a primary therapy for T cell-mediated autoimmune diseases. TCR-based immunotherapy after rapid identification of autoimmune disease-associated TCRs by CDR3 spectratyping can be applicable, not only to animal, but also to human autoimmune diseases whose pathomechanism is poorly understood.
Matsumoto
Y
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan. matyoh@tmin.ac.jp
Jee
Y
Y
Sugisaki
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009218:Myosins / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000473:pathology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000276:immunology
D016693:Receptors, Antigen, T-Cell, alpha-beta; C075784:T cell receptor Vbeta8; D019444:Vaccines, DNA; D010566:Virulence Factors, Bordetella; D009218:Myosins