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Regulation of the Expression of Adoptive Tumor Rejection Immunity by Recipient Cyclophosphamide-sensitive Cells¹

Departments of Microbiology [C. M. B., J. W. K., G. L. B.] and Pathology [J. W. K., G. L. B.], and Specialized Cancer Research Center, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033

Peritoneal exudate T-cells from rats immune to 13762A rat mammary tumor conferred specific tumor rejection immunity on normal recipients. The efficiency of systemic adoptive transfer of tumor rejection immunity with immune peritoneal exudate T-cells was improved by cyclophosphamide (CY) pretreatment of recipients. Optimal potentiation was obtained with a dose of 50 or 100 mg CY per kg body weight given the day before transfer. CY pretreatment of recipients was effective 1 to 3 days prior to transfer. The CY-potentiating effect was lost with longer intervals between CY administration and transfer, indicating recipient recovery. CY pretreatment enabled recipients to reject greater numbers (100 times) of tumor cells and inhibited tumor challenge established before systemic adoptive transfer. The CY-induced potentiation of systemic transfer of tumor immunity was reversed by i.v.-administered normal spleen. We concluded that CY-sensitive host regulatory cells restricted the expression of adoptive tumor rejection immunity. Control of the activity of these regulatory cells allows increased efficacy of effector T-lymphocytes in this system.

¹ Supported by National Cancer Institute Contract CB-33891, Grants R01 CA 29006 and CA 18450, and the Jake Gittlen Memorial Golf Tournament.

² Present address: Clinical Immunology Laboratory, North Carolina Memorial Hospital, Chapel Hill, N. C. 27514.

³ To whom requests for reprints should be addressed.

Received 10/ 6/81. Accepted 2/26/82.