The cooperation between two CD4 T cells induces tumor protective immunity in MUC.1 transgenic mice.
Immunity and tumor protection in mice transgenic for human MUC.1, a glycoprotein expressed in the majority of cancers of epithelial origin in humans, were induced by vaccination with B lymphocytes genetically programmed to activate MUC.1-specific CD4 T cells. Their activation required a functional cooperation between two Th cells, one specific for a self (MUC.1) and the other for a nonself T cell determinant. The immunological switch provided by Th-Th cooperation was sufficient to induce MUC.1-specific CD4 and CD8 T cell responses in MUC.1-transgenic mice, and protect them permanently from tumor growth. CD4 T cells specific for MUC.1 lacked cytolytic function, but produced IFN-gamma upon restimulation with Ag. We conclude that immunity against tumor self-Ags and tumor protection can be regulated exploiting an inherent property of the immune system.
Gerloni
Mara
M
Laboratory of Immunology, Department of Medicine and Cancer Center, University of California-San Diego, La Jolla, CA 92093, USA.
Castiglioni
Paola
P
Zanetti
Maurizio
M
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics* / Q000276:immunology*; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1; D009077:Mucins / Q000235:genetics* / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000941:Antigens; D000951:Antigens, Neoplasm; D006023:Glycoproteins; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins; D007371:Interferon-gamma