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Department of Immunology [W-Z. W., R. F-J., S. J. T.] and Breast Cancer Group [R. P.], Michigan Cancer Foundation, Detroit, Michigan 48201
The effect of growth of BALB/c C4 preneoplastic and neoplastic mammary lesions on the host T-cell repertoire was investigated. T-cells with specific Vß regions (Vß2, -6, -8.1-2, -11, and -14) in the T-cell receptors were enumerated in C4 hyperplastic alveolar nodule (HAN)-infiltrating lymphocytes and lymph node cells from both C4 HAN and C4 tumor-bearing mice by flow cytometry with Vß-specific monoclonal antibodies. Growth of C4 HAN and tumor induced selective deletion of peripheral Vß2+ T-cells. Elimination of Vß2+ T-cells [7.2 ± 0.8% (SD) of normal lymph node T-cells by C4 HAN was biphasic and irreversible. Approximately one-half of the Vß2+ T-cells were lost within the first month of C4 HAN implantation. Further reduction of Vß2+ T-cells took place after another 3 months, at which time the level of Vß2 was reduced to 1.2 ± 0.1% of the total T-cell population. Vß2 deletion occurred in BALB/c mice which had been implanted with C4 HAN at either 3 weeks or 2 months of age. Loss of Vß2+ T-cells was not reversed by removal of C4 HAN. C4 tumor also induced Vß2+ T-cell deletion. These results demonstrate a novel Vß2 deleting activity expressed by C4 mammary lesions and suggest that during mouse mammary tumorigenesis, a unique "superantigen" is expressed which can cause profound systemic changes in the T-cell repertoire.
1 This work was supported by National Cancer Institute Grant CA-42522 and the Concern Foundation.
2 To whom requests for reprints should be addressed, at Department of Immunology, Michigan Cancer Foundation, 110 E. Warren Ave., Detroit, MI 48201.
Received 4/ 1/91. Accepted 4/30/91.
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