PT  - JOURNAL ARTICLE
AU  - Wolchok, Jedd D.
AU  - Srinivasan, Roopa
AU  - Perales, Miguel-Angel
AU  - Houghton, Alan N.
AU  - Bowne, Wilbur B.
AU  - Blachere, Nathalie E.
TI  - Alternative roles for interferon-gamma in the immune response to DNA vaccines encoding related melanosomal antigens
DP  - 2001 Jan 01
TA  - Cancer Immunity Archive
PG  - 9
VI  - 1
IP  - 1
4099  - http://cancerimmunolres.aacrjournals.org/content/1/1/9.short
4100  - http://cancerimmunolres.aacrjournals.org/content/1/1/9.full
SO  - Cancer Immun2001 Jan 01; 1
AB  - 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. This article was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.