Split tolerance induced by immunotoxin in a rhesus kidney allograft model.
BACKGROUND: Renal allografts were performed in rhesus monkeys using FN18-CRM9, a potent immunotoxin capable of depleting T cells to less than 1% of baseline levels in blood and lymph nodes, as a preparative agent. We have recently reported that animals pretreated with FN18-CRM9 1 week before transplantation without further immunosuppression had prolonged graft survival time compared with control animals, and frequently became tolerant. METHODS: This report examines the alloimmune responses of recipient monkeys to the donor, including cytotoxic T lymphocyte precursor (CTLp) frequency, mixed lymphocyte response, and antidonor IgG response. RESULTS: CTLp frequencies declined significantly (P<0.01) after FN18-CRM9 treatment and renal transplantation. This decline in CTLp was initially nonspecific, as CTLp frequencies against third-party animals also declined (P<0.01). The decrease in CTLp was maintained in five of five animals tested 6 months after transplant. However, unresponsiveness was limited to the CTL arm of the immune response as antidonor IgG was detected in four of four animals tested, and the 5-day mixed lymphocyte response stimulation index and relative response were not significantly different before and after transplant. In long-term survivors (>150 days), an increase in anti-third-party CTLp was detected 1 month after grafting with third-party skin. No change was seen in the antidonor CTLp frequency after donor skin grafting, indicating that a specific defect in the antidonor CTL response had developed. CONCLUSIONS: These data suggest that FN18-CRM9 treatment of rhesus monkeys allows the development of specific down-regulation of antidonor CTL activity in renal allograft recipients.
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Related Subject Headings
- Transplantation, Homologous
- T-Lymphocytes, Helper-Inducer
- T-Lymphocytes, Cytotoxic
- T-Lymphocytes
- Surgery
- Skin Transplantation
- Macaca mulatta
- Lymphocyte Subsets
- Lymphocyte Culture Test, Mixed
- Kidney Transplantation
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Transplantation, Homologous
- T-Lymphocytes, Helper-Inducer
- T-Lymphocytes, Cytotoxic
- T-Lymphocytes
- Surgery
- Skin Transplantation
- Macaca mulatta
- Lymphocyte Subsets
- Lymphocyte Culture Test, Mixed
- Kidney Transplantation