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Protection against growth of MUC1/sec transfected mammary tumor cells is mediated by an effector cell with perforin-dependent cytotoxicity

  • T Fu
  • L Herbert
  • I Keydar
  • DM Lopez
Meeting abstract

Keywords

Nude Mouse Effector Cell Full Text Neomycin Spleen Cell 
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Full text

We have previously found that DA-3 mammary tumor cells transfected with the secreted form of the MUC1-gene (DA-3/sec) resulted in no tumor growth, whereas transfection with the neomycin vector alone (DA-3/neo) or with the transmembrane form of MUC-1 (DA-3/TM) did not change the growth characteristics of the DA-3 cells. Implantation of the DA-3/sec in nude mice resulted in tumor development, indicating that the immune response is a major cause of the lack of growth of these cells in immunologically intact mice. In vitro activated spleen cells from DA-3/sec-injected mice showed strong cytotoxicity against DA-3/sec, but not to DA-3, DA-3/neo or DA-3/TM cells. This cytotoxicity was clearly neutralized by in vivo administration of anti-CD3 monoclonal antibody, but not by anti-CD4 or anti-CD8 antibodies. Analysis of the mechanism of killing of the effector cells revealed that anti-Fas antibody did not affect the reaction. Furthermore, FasL-transfected EL-4 cells were not able to kill the DA-3 cells. In contrast, con-canomycin A, a perforin-specific inhibitor, greatly reduced the cytotoxicity of spleen cells from DA-3/sec-injected mice. These data suggest that a cell with a phenotype compatible to that of a NK T cell, may be responsible, at least in part, for the protection against the growth of DA-3/sec cells in immunocompetent mice.

Copyright information

© BioMed Central Ltd 2001

Authors and Affiliations

  • T Fu
    • 1
  • L Herbert
    • 1
  • I Keydar
    • 2
  • DM Lopez
    • 1
  1. 1.Department of Microbiology and ImmunologyUniversity of Miami School of MedicineMiamiUSA
  2. 2.Tel-Aviv UniversityTel-AvivIsrael

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