A reinvestigation of epidermal transplantation during chemical carcinogenesis.
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Biomedical subjects
Publications and source records attributed to D Steinmuller.
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Skin isografts from mice that were immunologically tolerant to allogeneic tissue had the ability to immunize isogeneic recipients against subsequent skin allografts. The immunizing isografts showed no gross signs of rejection themselves and appeared to be only the vehicles for transplantation antigen. It seems likely that allogeneic leukocytes derived from the spleen and bone marrow cells used to confer tolerance were contained in the skin of the tolerant mice and were transferred by the skin isografts in sufficient numbers to stimulate transplantation immunity.
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Epa-1-specific cytotoxic T lymphocytes (CTL) lyse epidermal cells (EC) of different Epa-1+ H-2k strains, such a AKR, CBA, C58, and RF, at different levels. We used an H-2Kk-specific monoclonal antibody (mAb) to test the hypothesis that this phenomenon is due to differences in the H-2-restricting element. Initially, we established the specificity of this mAb for the Epa-1-restricting element by demonstrating its capacity to inhibit the lysis of CBA EC by Epa-1-specific CTL. We then used it as the probe in a cellular radioimmunoassay to quantify the expression of the restricting element by EC of different H-2k strains. We found that C58 and RF EC bound significantly less of the mAb than did CBA EC. Although AKR also bound less of the mAb than did CBA EC, the difference was not statistically significant. To examine the generality of this phenomenon, we quantified the expression of Kk antigens on spleen cells (SC) of the same four strains. We found that RF SC, but not AKR or C58 SC, bound significantly less of the Kk mAb than did CBA SC. Thus, the differential CTL lysis of Epa-1+ EC of different strains probably reflects differences in expression of the H-2-restricting element rather than of the nominal antigen.
Renal transplantation was performed in a patient with a history of surgical excision for localized transitional cell carcinoma. The graft functioned well; however, metastatic transitional cell carcinoma developed following transplantation. The patient was treated sequentially with CISCA (cisplatin, Cytoxan [cyclophosphamide], and Adriamycin [doxorubicin hydrochloride]) and M-VAC (methotrexate, vinblastine, Adriamycin, and cisplatin) with no alteration in maintenance immunosuppression. Full-dose chemotherapy was well tolerated, with no impairment of renal function, and a demonstrable reduction in tumor burden was achieved. The patient ultimately died of metastatic disease but enjoyed an excellent quality of life throughout the post-transplant period.