Alternative roles for interferon-gamma in the immune response to DNA vaccines encoding related melanosomal antigens Journal Article
| Authors: | Wolchok, J. D.; Srinivasan, R.; Perales, M. A.; Houghton, A. N.; Bowne, W. B.; Blachere, N. E. |
| Article Title: | Alternative roles for interferon-gamma in the immune response to DNA vaccines encoding related melanosomal antigens |
| Abstract: | Tyrosinase-related proteins-1 and -2 (gp75/TRP-1 and TRP-2) are melanosomal membrane glycoproteins recognized by antibodies and T-cells from patients with melanoma. Xenogeneic DNA immunization against gp75/TRP-1 generates antibody-dependent tumor immunity and autoimmune depigmentation. In contrast xenogeneic TRP-2 DNA immunization induces immunity mediated by CD8+ T-cells. The role of IFN-gamma in the generation of tumor immunity and autoimmune depigmentation in these two models was investigated. No tumor protection and minimal depigmentation was observed after immunization with human TRP-2 DNA in mice deficient in IFN-gamma ligand. Repletion with recombinant murine IFN-gamma restored tumor immunity. Experiments using IL4 deficient mice demonstrated that tumor immunity was unaffected but that autoimmune depigmentation was potentially accelerated, consistent with down-modulation of autoimmunity against TRP-2 by IL4. In contrast, IFN-gamma was not required for the generation of immunity to gp75/TRP-1. In fact, exogenous IFN-gamma ablated autoantibody responses against gp75/TRP-1 after xenogeneic DNA immunization, consistent with a down-regulatory effect of IFN-gamma. These results show that immunity to TRP-2 following DNA immunization uses an IFN-gamma-dependent Th1 pathway, but immunity to gp75/TRP-1 is down-regulated by IFN-gamma. |
| Keywords: | genetics; interferon; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; metabolism; mouse mutant; animals; mice; mice, knockout; cells, cultured; melanoma; mice, mutant strains; tumor cells, cultured; tumor antigen; mice, inbred c57bl; physiology; c57bl mouse; biosynthesis; immunology; chemistry; dna; antigens, neoplasm; gamma interferon; cancer vaccine; cell culture; cancer vaccines; cd4+ t lymphocyte; cd4-positive t-lymphocytes; dna, neoplasm; dna vaccine; autoantibody; pregnancy proteins; vaccines, dna; autoantibodies; antibodies, neoplasm; secretion; cancer antibody; dopachrome isomerase; isomerase; intramolecular oxidoreductases; interferon type i; interferon type ii; placenta protein; humans; human; article; trophoblast protein 1 |
| Journal Title: | Cancer Immunity |
| Volume: | 1 |
| ISSN: | 1424-9634 |
| Publisher: | Academy of Cancer Immunology |
| Date Published: | 2001-08-16 |
| Start Page: | 9 |
| Language: | English |
| PUBMED: | 12747770 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Citation Impact
Related MSK Work