Coupling and uncoupling of tumor immunity and autoimmunity Journal Article
| Authors: | Bowne, W. B.; Srinivasan, R.; Wolchok, J. D.; Hawkins, W. G.; Blachere, N. E.; Dyall, R.; Lewis, J. J.; Houghton, A. N. |
| Article Title: | Coupling and uncoupling of tumor immunity and autoimmunity |
| Abstract: | Self-antigens, in the form of differentiation antigens, are commonly recognized by the immune system on melanoma and other cancers. We have shown previously that active immunization of mice against the melanocyte differentiation antigen, a tyrosinase-related protein (TRP) gp75(TRP-1) (the brown locus protein) expressed by melanomas, could induce tumor immunity and autoimmunity manifested as depigmentation. In this system, tumor immunity and autoimmunity were mediated by autoantibodies. Here, we characterize immunity against another tyrosinase family glycoprotein TRP-2 (the slaty locus protein), using the same mouse model and method of immunization. As observed previously for gp75(TRP-1), immunity was induced by DNA immunization against a xenogeneic form of TRP-2, but not against the syngeneic gene, and depended on CD4+ cells. Immunization against TRP-2 induced autoantibodies and autoreactive cytotoxic T cells. In contrast to immunization against gp75(TRp- 1), both tumor immunity and autoimmunity required CD8+ T cells, but not antibodies. Only autoimmunity required perforin, whereas tumor immunity proceeded in the absence of perforin. Thus, immunity induced against two closely related autoantigens that are highly conserved throughout vertebrate evolution involved qualitatively different mechanisms, i.e., antibody versus CD8+ T cell. However, both pathways led to tumor immunity and identical phenotypic manifestations of autoimmunity. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animals; mice; mice, knockout; melanoma; melanocyte; lung neoplasms; animal experiment; animal model; tumor cells, cultured; transfection; mice, inbred c57bl; immunotherapy; membrane glycoproteins; antibody response; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; plasmid; melanoma, experimental; transplantation, heterologous; killer cells, natural; tumor immunity; perforin; autoimmunity; neoplasm transplantation; autoantibodies; lymphocyte depletion; antibody formation; immunization; transplantation, isogeneic; t cell; intramolecular oxidoreductases; tumor immunology; pore forming cytotoxic proteins; humans; female; priority journal; article; beta 2-microglobulin; tyrosinase-related protein |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 190 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1999-12-06 |
| Start Page: | 1717 |
| End Page: | 1722 |
| Language: | English |
| DOI: | 10.1084/jem.190.11.1717 |
| PUBMED: | 10587362 |
| PROVIDER: | scopus |
| PMCID: | PMC2195744 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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