Induction of cytotoxic T lymphocytes specific for paraneoplastic cerebellar degeneration-associated antigen in vivo by DNA immunization.
Paraneoplastic cerebellar degeneration associated with gynecological and breast malignancies (PCD) is known to develop autoantibodies and autoreactive cytotoxic T lymphocytes (CTLs) specific for a cytoplasmic protein of Purkinje cells PCD17/cdr2, in the blood of patients. The functional roles of these antibodies and CTLs in the pathogenesis of PCD are unknown. Induction of immune response to this antigen in experimental animals should be useful to clarify the immune mechanisms in PCD patients. We immunized Balb/c mice with naked DNA, which is encoded human PCD17 neural protein in an eukaryotic expression plasmid under control of CMV promoter, and explored whether or not humoral and cell-mediated immune responses against PCD17 could be induced in vivo. We show that DNA immunization with naked pcd17 cDNA could induce autoantibodies against the cytoplasmic protein of Purkinje cells and CTLs could lyse syngenic myeloma cells pulsed with H-2K-restricted PCD17 peptide. In spite of the generation of anti-Purkinje cell antibodies and PCD17-specific CTLs in vivo, neither clinical nor pathological changes consistent with significant cerebellar degeneration have been detected.
Sakai
K
K
Department of Neurology, Kanazawa Medical University, Ishikawa, Japan. ksakai@kanazawa-med.ac.jp
Shirakawa
T
T
Kitagawa
Y
Y
Li
Y
Y
Hirose
G
G
D000818:Animals; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D020362:Paraneoplastic Cerebellar Degeneration / Q000276:immunology*; D011689:Purkinje Cells / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D001323:Autoantibodies; C095184:CDR2 protein, human; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D004247:DNA