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Department of Immunology, Breast Cancer Program, Michigan Cancer Foundation, Detroit, Michigan 48201 [R. G., H. W., W. W.]; Department of Biology, F. Hoffman-LaRoche Ltd., Basel, Switzerland [H. B.]; and Department of Neuroimmunology, Max-Planck-Institut für Psychiatrie, Munich, Germany [A. I.]
Lymphocytic infiltrates of BALB/c C4 hyperplastic alveolar nodule (HAN) have elevated natural killer (NK) activity, which correlates positively with the progression of C4 HAN to tumor. C4 HAN produces an infectious mouse mammary tumor virus, MMTV(C4), which encodes a superantigen that activates and deletes T-cells with the Vß2 segment in the T-cell receptor. In this report, NK activation by both MMTV(C4) and MMTV(C4) superantigen was tested. NK activity was measured in naive BALB/c mice, BALB/c mice depleted of Vß2+ T-cell, or Vß2-transgenic mice after they received injections of either purified MMTV(C4) or MMTV(C4)-infected splenocytes. Elevated NK activity was observed in BALB/c mice receiving MMTV(C4) or MMTV(C4)-infected splenocytes. Depletion of Vß2+, but not Vß8+, T-cells by specific anti-Vß hybridoma before injection of MMTV(C4)-infected cells reduced but did not eliminate NK activation. NK activation in Vß2-transgenic mice occurred before massive CD4 T-cell deletion took place and was more pronounced than that in the nontransgenic littermates. These results indicate that MMTV activates NK cells through superantigen-dependent and -independent pathways and supports the role of MMTV(C4) in the augmented NK activity observed in C4 HAN infiltrates. The progression of C4 HAN to tumor represents a model system for the analysis of how tumorigenesis may be affected by lesion-associated viruses.
1 This work was supported by National Cancer Institute Grants CA-42522 and T32 CA09531.
2 To whom requests for reprints should be addressed, at Department of Immunology, Breast Cancer Program, Michigan Cancer Foundation, 110 E. Warren Avenue, Detroit, MI 48201.
Received 9/10/93. Accepted 1/11/94.
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