Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats.
- 1 April 1986
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 83 (8) , 2624-2627
- https://doi.org/10.1073/pnas.83.8.2624
Abstract
The mouse hybridoma ART 18 monoclonal antibody (mAb), which binds to the rat interleukin 2 (IL-2) receptor, was studied for its effect on heterotopic cardiac allograft survival in two histoincompatible inbred rat strain combinations. Treatment with ART 18 mAb for 10 days after transplantation prolonged allograft survival in a dose-dependent fashion up to about 3 weeks (acute rejection normally occurs within 8 days). ART 18 mAb therapy started at 5 days after transplantation (the time of major rejection activity) abrogated acute rejection and extended the survival to about 18 days. The dense cellular infiltrate noted histologically in acute rejection had virtually disappeared after ART 18 mAb treatment. Thus, IL-2 receptor-targeted therapy can be successfully used to prevent and/or treat acute rejection. When spleen cells from antibody-treated recipients bearing well-functioning allografts were adoptively transferred to normal untreated rats that received cardiac allografts 24 hr later, the survival of donor-specific, but not third-party, test cardiac allografts was prolonged significantly; this supports the idea that ART 18 mAb induced "sparing" of suppressor T lymphocytes. Combining infusion of ART 18 mAb with exogenous IL-2-rich conditioned medium produced the same effect as if the mAb alone had been administered, suggesting that an excess of IL-2 does not prevent binding of ART 18 mAb to IL-2 receptor-bearing cells in vivo. These results support the important role of the IL-2 receptor-bearing cells in the mechanism of allograft rejection; they may represent an important target for immunosuppression in clinical organ transplantation.This publication has 28 references indexed in Scilit:
- Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell.The Journal of Experimental Medicine, 1985
- Expression of Tac antigen on activated normal human B cells.The Journal of Experimental Medicine, 1984
- Restoration of allograft responsiveness in B ratsCellular Immunology, 1984
- Partial characterization of the putative rat interleukin 2 receptorEuropean Journal of Immunology, 1984
- RESTORATION OF ALLOGRAFT RESPONSIVENESS IN B RATSTransplantation, 1983
- ROLE OF THYMUS-DERIVED AND THYMUS-INDEPENDENT CELLS IN MURINE SKIN ALLOGRAFT REJECTIONTransplantation, 1982
- T cell growth factor receptors. Quantitation, specificity, and biological relevanceThe Journal of Experimental Medicine, 1981
- Studies on T lymphocyte activation II. The target cells for concanavalin A‐induced growth factorsEuropean Journal of Immunology, 1979
- Hybrid cell lines secreting monoclonal antibody specific for major histocompatibility antigens of the mouseNature, 1978
- Continuous cultures of fused cells secreting antibody of predefined specificityNature, 1975